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Wang, Li, Chao-Chao Yu, Xin-Yuan Liu, Xiao-Ni Deng, Qing Tian und Yan-Jun Du. „Epigenetic Modulation of Microglia Function and Phenotypes in Neurodegenerative Diseases“. Neural Plasticity 2021 (29.05.2021): 1–13. http://dx.doi.org/10.1155/2021/9912686.
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Microglia-mediated neuroinflammation is one of the most remarkable hallmarks of neurodegenerative diseases (NDDs), including AD, PD, and ALS. Accumulating evidence indicates that microglia play both neuroprotective and detrimental roles in the onset and progression of NDDs. Yet, the specific mechanisms of action surrounding microglia are not clear. Modulation of microglia function and phenotypes appears to be a potential strategy to reverse NDDs. Until recently, research into the epigenetic mechanisms of diseases has been gradually developed, making it possible to elucidate the molecular mechanisms underlying the epigenetic regulation of microglia in NDDs. This review highlights the function and phenotypes of microglia, elucidates the relationship between microglia, epigenetic modifications, and NDDs, as well as the possible mechanisms underlying the epigenetic modulation of microglia in NDDs with a focus on potential intervention strategies.
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Sharifi-Rad, Mehdi, Chintha Lankatillake, Daniel A. Dias, Anca Oana Docea, Mohamad Fawzi Mahomoodally, Devina Lobine, Paul L. Chazot et al. „Impact of Natural Compounds on Neurodegenerative Disorders: From Preclinical to Pharmacotherapeutics“. Journal of Clinical Medicine 9, Nr. 4 (08.04.2020): 1061. http://dx.doi.org/10.3390/jcm9041061.
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Among the major neurodegenerative disorders (NDDs), Alzheimer’s disease (AD) and Parkinson’s disease (PD), are a huge socioeconomic burden. Over many centuries, people have sought a cure for NDDs from the natural herbals. Many medicinal plants and their secondary metabolites are reported with the ability to alleviate the symptoms of NDDs. The major mechanisms identified, through which phytochemicals exert their neuroprotective effects and potential maintenance of neurological health in ageing, include antioxidant, anti-inflammatory, antithrombotic, antiapoptotic, acetylcholinesterase and monoamine oxidase inhibition and neurotrophic activities. This article reviews the mechanisms of action of some of the major herbal products with potential in the treatment of NDDs according to their molecular targets, as well as their regional sources (Asia, America and Africa). A number of studies demonstrated the beneficial properties of plant extracts or their bioactive compounds against NDDs. Herbal products may potentially offer new treatment options for patients with NDDs, which is a cheaper and culturally suitable alternative to conventional therapies for millions of people in the world with age-related NDDs.
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Guo, Li, Bing-Xiao Li, Mei Deng, Fang Wen, Jian-Hui Jiang, Yue-Qiu Tan, Yuan-Zong Song et al. „Etiological Analysis of Neurodevelopmental Disabilities: Single-Center Eight-Year Clinical Experience in South China“. Journal of Biomedicine and Biotechnology 2011 (2011): 1–11. http://dx.doi.org/10.1155/2011/318616.
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Etiology determination of neurodevelopmental disabilities (NDDs) currently remains a worldwide common challenge on child health. We herein reported the etiology distribution feature in a cohort of 285 Chinese patients with NDDs. Although concrete NDD etiologies in 48.4% of the total patients could not be identified, genetic diseases (with the proportion of 35.8% in the total cases) including inborn errors of metabolism (IEM) and congenital dysmorphic diseases, constituted the commonest etiology category for NDDs in this study. The two key experimental technologies in pediatric metabolomics, gas chromatography-mass spectrometry (GC-MS), and tandem mass spectrometry (MS-MS), proved to be substantially helpful for the exploration of the NDD etiologies in this clinical investigation. The findings in this paper provided latest epidemiologic information on the etiology distribution of NDDs in Chinese, and the syndromic NDDs caused by citrin deficiency and the novel chromosomal karyotype, respectively, further expanded the etiology spectrum of NDDs.
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Aravamuthan, Bhooma R., Michael Shevell, Young-Min Kim, Jenny L. Wilson, Jennifer A. O'Malley, Toni S. Pearson, Michael C. Kruer et al. „Role of child neurologists and neurodevelopmentalists in the diagnosis of cerebral palsy“. Neurology 95, Nr. 21 (12.10.2020): 962–72. http://dx.doi.org/10.1212/wnl.0000000000011036.
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ObjectiveTo contextualize the role of child neurologists and neurodevelopmentalists (CNs/NDDs) in cerebral palsy (CP) care, we review the changing landscape of CP diagnosis and survey stakeholder CNs/NDDs regarding their roles in CP care.MethodsThe optimal roles of the multiple specialties involved in CP care are currently unclear, particularly regarding CP diagnosis. We developed recommendations regarding the role of CNs/NDDs noting (1) increasing complexity of CP diagnosis given a growing number of genetic etiologies and treatable motor disorders that can be misdiagnosed as CP and (2) the views of a group of physician stakeholders (CNs/NDDs from the Child Neurology Society Cerebral Palsy Special Interest Group).ResultsCNs/NDDs felt that they were optimally suited to diagnose CP. Many (76%) felt that CNs/NDDs should always be involved in CP diagnosis. However, 42% said that their patients with CP were typically not diagnosed by CNs/NDDs, and 18% did not receive referrals to establish the diagnosis of CP at all. CNs/NDDs identified areas of their expertise critical for CP diagnosis including knowledge of the neurologic examination across development and early identification of features atypical for CP. This contrasts with their views on CP management, where CNs/NDDs felt that they could contribute to the medical team, but were necessary primarily when neurologic coexisting conditions were present.DiscussionGiven its increasing complexity, we recommend early referral for CP diagnosis to a CN/NDD or specialist with comparable expertise. This contrasts with current consensus guidelines, which either do not address or do not recommend specific specialist referral for CP diagnosis.
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Berglund Melendez, Andrea, Maria Malmsten, Eva-Lena Einberg, Eva K. Clausson und Pernilla Garmy. „Supporting Students with Neurodevelopment Disorders in School Health Care—School Nurses’ Experiences“. International Journal of Environmental Research and Public Health 17, Nr. 16 (09.08.2020): 5752. http://dx.doi.org/10.3390/ijerph17165752.
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Students with neurodevelopmental disorders (NDDs) are present in every school, and most likely, there are a few students in every class. School health care is responsible for providing support to all students, especially those with special needs. The aim of the study was to describe school nurses’ experiences of supporting students with NDDs. A qualitative method consisting of seven focus group interviews (that included a total of 35 school nurses) in Southern Sweden was conducted. Three themes were identified in the findings: helping students with NDDs to interpret sensations, detecting early signs of distress among students with NDDs, and using an inclusive design for health education. This study highlights the importance of school nurses in identifying the needs of students with NDDs and promotes a person-centered approach to achieve a healthy and safe learning environment for all students.
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Soni, Neetu, Manish Ora, Girish Bathla, Chandana Nagaraj, Laura L. Boles Ponto, Michael M. Graham, Jitender Saini und Yusuf Menda. „Multiparametric magnetic resonance imaging and positron emission tomography findings in neurodegenerative diseases: Current status and future directions“. Neuroradiology Journal 34, Nr. 4 (05.03.2021): 263–88. http://dx.doi.org/10.1177/1971400921998968.
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Neurodegenerative diseases (NDDs) are characterized by progressive neuronal loss, leading to dementia and movement disorders. NDDs broadly include Alzheimer’s disease, frontotemporal lobar degeneration, parkinsonian syndromes, and prion diseases. There is an ever-increasing prevalence of mild cognitive impairment and dementia, with an accompanying immense economic impact, prompting efforts aimed at early identification and effective interventions. Neuroimaging is an essential tool for the early diagnosis of NDDs in both clinical and research settings. Structural, functional, and metabolic imaging modalities, including magnetic resonance imaging (MRI) and positron emission tomography (PET), are widely available. They show encouraging results for diagnosis, monitoring, and treatment response evaluation. The current review focuses on the complementary role of various imaging modalities in relation to NDDs, the qualitative and quantitative utility of newer MRI techniques, novel radiopharmaceuticals, and integrated PET/MRI in the setting of NDDs.
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Cory-Slechta, Deborah, Marissa Sobolewski und Günter Oberdörster. „Air Pollution-Related Brain Metal Dyshomeostasis as a Potential Risk Factor for Neurodevelopmental Disorders and Neurodegenerative Diseases“. Atmosphere 11, Nr. 10 (14.10.2020): 1098. http://dx.doi.org/10.3390/atmos11101098.
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Increasing evidence links air pollution (AP) exposure to effects on the central nervous system structure and function. Particulate matter AP, especially the ultrafine (nanoparticle) components, can carry numerous metal and trace element contaminants that can reach the brain in utero and after birth. Excess brain exposure to either essential or non-essential elements can result in brain dyshomeostasis, which has been implicated in both neurodevelopmental disorders (NDDs; autism spectrum disorder, schizophrenia, and attention deficit hyperactivity disorder) and neurodegenerative diseases (NDGDs; Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, and amyotrophic lateral sclerosis). This review summarizes the current understanding of the extent to which the inhalational or intranasal instillation of metals reproduces in vivo the shared features of NDDs and NDGDs, including enlarged lateral ventricles, alterations in myelination, glutamatergic dysfunction, neuronal cell death, inflammation, microglial activation, oxidative stress, mitochondrial dysfunction, altered social behaviors, cognitive dysfunction, and impulsivity. Although evidence is limited to date, neuronal cell death, oxidative stress, and mitochondrial dysfunction are reproduced by numerous metals. Understanding the specific contribution of metals/trace elements to this neurotoxicity can guide the development of more realistic animal exposure models of human AP exposure and consequently lead to a more meaningful approach to mechanistic studies, potential intervention strategies, and regulatory requirements.
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Gupta, Swapnil, Panpan You, Tanima SenGupta, Hilde Nilsen und Kulbhushan Sharma. „Crosstalk between Different DNA Repair Pathways Contributes to Neurodegenerative Diseases“. Biology 10, Nr. 2 (19.02.2021): 163. http://dx.doi.org/10.3390/biology10020163.
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Genomic integrity is maintained by DNA repair and the DNA damage response (DDR). Defects in certain DNA repair genes give rise to many rare progressive neurodegenerative diseases (NDDs), such as ocular motor ataxia, Huntington disease (HD), and spinocerebellar ataxias (SCA). Dysregulation or dysfunction of DDR is also proposed to contribute to more common NDDs, such as Parkinson’s disease (PD), Alzheimer’s disease (AD), and Amyotrophic Lateral Sclerosis (ALS). Here, we present mechanisms that link DDR with neurodegeneration in rare NDDs caused by defects in the DDR and discuss the relevance for more common age-related neurodegenerative diseases. Moreover, we highlight recent insight into the crosstalk between the DDR and other cellular processes known to be disturbed during NDDs. We compare the strengths and limitations of established model systems to model human NDDs, ranging from C. elegans and mouse models towards advanced stem cell-based 3D models.
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Gulati, Sheffali. „Neurodevelopmental Disorders: The Journey, the Dreams and their Realization“. Annals of the National Academy of Medical Sciences (India) 53, Nr. 01 (Januar 2017): 030–35. http://dx.doi.org/10.1055/s-0040-1712742.
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ABSTRACTNeuro Developmental Disorders (NDDs) are associated with significant morbidity. This involves early identification of the disorder, the correct management of the disorder and associated disabilities. In India, the paucity of trained personnel and lack of knowledge about these disorders has been instrumental in inadequate management and recognition of these NDDs. The Child Neurology Division, Department of Pediatrics at All India Institute of Medical Sciences has made few noteworthy and meaningful contributions in these aspects: devising a DM curriculum for pediatric neurology, developing indigenous tools for diagnosing these NDDs and performing relevant research. These endeavors would go a long way in serving the children with NDDs.
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Ozlu, Can, Rachel M. Bailey, Sarah Sinnett und Kimberly D. Goodspeed. „Gene Transfer Therapy for Neurodevelopmental Disorders“. Developmental Neuroscience 43, Nr. 3-4 (2021): 230–40. http://dx.doi.org/10.1159/000515434.
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Neurodevelopmental disorders (NDDs) include a broad spectrum of disorders that disrupt normal brain development. Though some NDDs are caused by acquired insults (i.e., toxic or infectious encephalopathy) or may be cryptogenic, many NDDs are caused by variants in a single gene or groups of genes that disrupt neuronal development or function. In this review, we will focus on those NDDs with a genetic etiology. The exact mechanism, timing, and progression of the molecular pathology are seldom well known; however, the abnormalities in development typically manifest in similar patterns such as delays or regression in motor function, social skills, and language or cognitive abilities. Severity of impairment can vary widely. At present, only symptomatic treatments are available to manage seizures and behavioral problems commonly seen in NDDs. In recent years, there has been a rapid expansion of research into gene therapy using adeno-associated viruses (AAVs). Using AAVs as vectors to replace the non- or dysfunctional gene in vivo is a relatively simple model which has created an unprecedented opportunity for the future of NDD treatment. Advances in this field are of paramount importance as NDDs lead to a massive lifelong burden of disease on the affected individuals and families. In this article, we review the unique advantages and challenges of AAV gene therapies. We then look at potential applications of gene therapy for 3 of the more common NDDs (Rett syndrome, fragile X syndrome, and Angelman syndrome), as well as 2 less common NDDs (<i>SLC13A5</i> deficiency disorder and <i>SLC6A1</i>-related disorder). We will review the available natural history of each disease and current state of preclinical studies including a discussion on the application of AAV gene therapies for each disease.
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Gunaseelan, Vinusha, Patricia Parkin, Imaan Bayoumi, Patricia Jiang, Alexandra Medline, Michael Osmond, Catherine Birken, Jonathon Maguire und Cory Borkhoff. „EVALUATING THE PREDICTIVE VALIDITY OF THE NIPISSING DISTRICT DEVELOPMENTAL SCREEN IN PRIMARY CARE SETTINGS AT THE 18-MONTH HEALTH SUPERVISION VISIT“. Paediatrics & Child Health 23, suppl_1 (18.05.2018): e37-e37. http://dx.doi.org/10.1093/pch/pxy054.096.
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Abstract BACKGROUND The Canadian Paediatric Society (CPS) recommends that every Canadian physician caring for young children provide an enhanced 18-month well-baby visit including the use of a developmental screening tool, such as the Nipissing District Developmental Screen (NDDS). The Province of Ontario implemented an enhanced 18-month well-baby visit specifically emphasizing the NDDS, which is now widely used in Ontario primary care. However, the diagnostic accuracy of the NDDS in identifying early developmental delays in real-world clinical settings is unknown. OBJECTIVES To assess the predictive validity of the NDDS in primary care for identifying developmental delay and prompting a specialist referral at the 18-month health supervision visit. DESIGN/METHODS This was a prospective longitudinal cohort study enrolling healthy children from primary care practices. Parents completed the 18-month NDDS during their child’s scheduled health supervision visit between January 2012 and February 2015. Using a standardized data collection form, research personnel abstracted data from the child’s health records regarding the child’s developmental outcomes following the 18-month assessment. Data collected included confirmed diagnoses of a development delay, specialist referrals, family history, and interventions. Research personnel were blind to the results of the NDDS. We assessed the diagnostic test properties of the NDDS with a confirmed diagnosis of developmental delay as the criterion measure. The specificity, sensitivity, positive predictive value, and negative predictive value were calculated, with 95% confidence intervals. RESULTS We included 255 children with a mean age of 18.5 months (range, 17.5–20.6) and 139 (55%) were male. 102 (40%) screened positive (1+ flag result on their NDDS). A total of 48 (19%) children were referred, and 23 (9%) had a confirmed diagnosis of a developmental delay (speech and language: 14; gross motor: 4; autism spectrum disorder: 3; global developmental delay: 1; developmental delay: 1). The sensitivity was 74% (95% CI: 52–90%), specificity was 63% (95% CI: 57–70%), positive predictive value was 17% (95% CI:10–25%), and the negative predictive value was 96% (95% CI: 92–99%). CONCLUSION For developmental screening tools, sensitivity between 70%-80% and specificity of 80% have been suggested. The NDDS has moderate sensitivity and specificity in identifying developmental delay at the 18-month health supervision visit. The 1+NDDS flag cut-point may lead to overdiagnosis with more children with typical development being referred, leading to longer wait times for specialist referrals among children in need. Future work includes investigating the diagnostic accuracy of combining the NDDS with other screening tools.
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Zhang, Yi, Tao Wang, Yan Wang, Kun Xia, Jinchen Li und Zhongsheng Sun. „Targeted sequencing and integrative analysis to prioritize candidate genes in neurodevelopmental disorders“. Molecular Neurobiology 58, Nr. 8 (15.04.2021): 3863–73. http://dx.doi.org/10.1007/s12035-021-02377-y.
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AbstractNeurodevelopmental disorders (NDDs) are a group of diseases characterized by high heterogeneity and frequently co-occurring symptoms. The mutational spectrum in patients with NDDs is largely incomplete. Here, we sequenced 547 genes from 1102 patients with NDDs and validated 1271 potential functional variants, including 108 de novo variants (DNVs) in 78 autosomal genes and seven inherited hemizygous variants in six X chromosomal genes. Notably, 36 of these 78 genes are the first to be reported in Chinese patients with NDDs. By integrating our genetic data with public data, we prioritized 212 NDD candidate genes with FDR < 0.1, including 17 novel genes. The novel candidate genes interacted or were co-expressed with known candidate genes, forming a functional network involved in known pathways. We highlighted MSL2, which carried two de novo protein-truncating variants (p.L192Vfs*3 and p.S486Ifs*11) and was frequently connected with known candidate genes. This study provides the mutational spectrum of NDDs in China and prioritizes 212 NDD candidate genes for further functional validation and genetic counseling.
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Sales, Prandi, Castro, Leal, Cunha, Kuca und Ramalho. „Recent Developments in Metal-Based Drugs and Chelating Agents for Neurodegenerative Diseases Treatments“. International Journal of Molecular Sciences 20, Nr. 8 (12.04.2019): 1829. http://dx.doi.org/10.3390/ijms20081829.
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The brain has a unique biological complexity and is responsible for important functions in the human body, such as the command of cognitive and motor functions. Disruptive disorders that affect this organ, e.g. neurodegenerative diseases (NDDs), can lead to permanent damage, impairing the patients’ quality of life and even causing death. In spite of their clinical diversity, these NDDs share common characteristics, such as the accumulation of specific proteins in the cells, the compromise of the metal ion homeostasis in the brain, among others. Despite considerable advances in understanding the mechanisms of these diseases and advances in the development of treatments, these disorders remain uncured. Considering the diversity of mechanisms that act in NDDs, a wide range of compounds have been developed to act by different means. Thus, promising compounds with contrasting properties, such as chelating agents and metal-based drugs have been proposed to act on different molecular targets as well as to contribute to the same goal, which is the treatment of NDDs. This review seeks to discuss the different roles and recent developments of metal-based drugs, such as metal complexes and metal chelating agents as a proposal for the treatment of NDDs.
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Li, Kuokuo, Zhengbao Ling, Tengfei Luo, Guihu Zhao, Qiao Zhou, Xiaomeng Wang, Kun Xia, Jinchen Li und Bin Li. „Cross-Disorder Analysis of De Novo Variants Increases the Power of Prioritising Candidate Genes“. Life 11, Nr. 3 (12.03.2021): 233. http://dx.doi.org/10.3390/life11030233.
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De novo variants (DNVs) are critical to the treatment of neurodevelopmental disorders (NDDs). However, effectively identifying candidate genes in small cohorts is challenging in most NDDs because of high genetic heterogeneity. We hypothesised that integrating DNVs from multiple NDDs with genetic similarity can significantly increase the possibility of prioritising the candidate gene. We catalogued 66,186 coding DNVs in 50,028 individuals with nine types of NDDs in cohorts with sizes spanning from 118 to 31,260 from Gene4Denovo database to validate this hypothesis. Interestingly, we found that integrated DNVs can effectively increase the number of prioritised candidate genes for each disorder. We identified 654 candidate genes including 481 shared candidate genes carrying putative functional variants in at least two disorders. Notably, 13.51% (65/481) of shared candidate genes were prioritised only via integrated analysis including 44.62% (29/65) genes validated in recent large cohort studies. Moreover, we estimated that more novel candidate genes will be prioritised with the increase in cohort size, in particular for some disorders with high putative functional DNVs per individual. In conclusion, integrated DNVs may increase the power of prioritising candidate genes, which is important for NDDs with small cohort size.
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Penna, Eduardo, Amelia Pizzella, Fabiano Cimmino, Giovanna Trinchese, Gina Cavaliere, Angela Catapano, Ivana Allocca et al. „Neurodevelopmental Disorders: Effect of High-Fat Diet on Synaptic Plasticity and Mitochondrial Functions“. Brain Sciences 10, Nr. 11 (31.10.2020): 805. http://dx.doi.org/10.3390/brainsci10110805.
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Neurodevelopmental disorders (NDDs) include diverse neuropathologies characterized by abnormal brain development leading to impaired cognition, communication and social skills. A common feature of NDDs is defective synaptic plasticity, but the underlying molecular mechanisms are only partially known. Several studies have indicated that people’s lifestyles such as diet pattern and physical exercise have significant influence on synaptic plasticity of the brain. Indeed, it has been reported that a high-fat diet (HFD, with 30–50% fat content), which leads to systemic low-grade inflammation, has also a detrimental effect on synaptic efficiency. Interestingly, metabolic alterations associated with obesity in pregnant woman may represent a risk factor for NDDs in the offspring. In this review, we have discussed the potential molecular mechanisms linking the HFD-induced metabolic dysfunctions to altered synaptic plasticity underlying NDDs, with a special emphasis on the roles played by synaptic protein synthesis and mitochondrial functions.
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Schaffert, Larissa-Nele, und Wayne G. Carter. „Do Post-Translational Modifications Influence Protein Aggregation in Neurodegenerative Diseases: A Systematic Review“. Brain Sciences 10, Nr. 4 (11.04.2020): 232. http://dx.doi.org/10.3390/brainsci10040232.
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The accumulation of abnormal protein aggregates represents a universal hallmark of neurodegenerative diseases (NDDs). Post-translational modifications (PTMs) regulate protein structure and function. Dysregulated PTMs may influence the propensity for protein aggregation in NDD-proteinopathies. To investigate this, we systematically reviewed the literature to evaluate effects of PTMs on aggregation propensity for major proteins linked to the pathogenesis and/or progression of NDDs. A search of PubMed, MEDLINE, EMBASE, and Web of Science Core Collection was conducted to retrieve studies that investigated an association between PTMs and protein aggregation in seven NDDs: Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS), spinocerebellar ataxias, transmissible spongiform encephalopathy, and multiple sclerosis. Together, 1222 studies were identified, of which 69 met eligibility criteria. We identified that the following PTMs, in isolation or combination, potentially act as modulators of proteinopathy in NDDs: isoaspartate formation in Aβ, phosphorylation of Aβ or tau in AD; acetylation, 4-hydroxy-2-neonal modification, O-GlcNAcylation or phosphorylation of α-synuclein in PD; acetylation or phosphorylation of TAR DNA-binding protein-43 in ALS, and SUMOylation of superoxide dismutase-1 in ALS; and phosphorylation of huntingtin in HD. The potential pharmacological manipulation of these aggregation-modulating PTMs represents an as-yet untapped source of therapy to treat NDDs.
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Caldani, Simona, Moetez Baghdadi, Ana Moscoso, Eric Acquaviva, Christophe-Loïc Gerard, Vincenzo Marcelli, Hugo Peyre, Paola Atzori, Richard Delorme und Maria Pia Bucci. „Vestibular Functioning in Children with Neurodevelopmental Disorders Using the Functional Head Impulse Test“. Brain Sciences 10, Nr. 11 (20.11.2020): 887. http://dx.doi.org/10.3390/brainsci10110887.
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Several studies in children with neurodevelopmental disorders (NDDs) including autism spectrum disorders (ASDs), reading impairment, or attention deficit/hyperactive disorder (ADHD) pointed toward a potential dysfunction of the vestibular system, specifically in its complex relationship with the cerebellum. The aim of the present study was to test the functional vestibulo-ocular reflex (VOR) responses in children with NDDs to measure functional performance of the vestibular system. The VOR is specifically involved in this stabilization of the image on the retina during rapid movements of the head. To perform this study, four groups of children with ASD, ADHD, reading impairment, and with neurotypical development (TD) were enrolled (n = 80). We performed the functional head impulse test (fHIT), which measured the percentage of correct responses by asking the child to identify an optotype briefly presented during passive head impulse in each direction of each semicircular canal plane. We observed significantly lower correct answers in children with NDDs compared with those with TD (p < 0.0001). Surprisingly, there was no significant difference between the three groups of children with NDDs. Our study fostered preliminary evidence suggesting altered efficiency of vestibular system in children with NDDs. VOR abnormalities estimated using the fHIT could be used as a proxy of NDD impairments in children, and represent a potential biomarker.
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Volcho, Konstantin P., Sergey S. Laev, Ghulam Md Ashraf, Gjumrakch Aliev und Nariman F. Salakhutdinov. „Application of Monoterpenoids and their Derivatives for Treatment of Neurodegenerative Disorders“. Current Medicinal Chemistry 25, Nr. 39 (17.01.2019): 5327–46. http://dx.doi.org/10.2174/0929867324666170112101837.
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Neurodegenerative disorders (NDDs) like Alzheimer's disease, Parkinson’s disease and Huntington’s disease are a heterogeneous group of disorders with the progressive and severe loss of neurons. There are no full proof cures for these diseases, and only medicines are available that can alleviate some of the symptoms. Developing effective treatments for the NDDs is a difficult but necessary task. Hence, the investigation of monoterpenoids which modulate targets applicable to many NDDs is highly relevant. Many monoterpenoids have demonstrated promising neuroprotective activity mediated by various systems. It can form the basis for elaboration of agents which will be useful both for the alleviation of symptoms of NDDs and for the treatment of diseases progression and also for prevention of neurodegeneration. The further developments including detections of monoterpenoids and their derivatives with high neuroprotective or neurotrophic activity as well as the results of qualified clinical trials are needed to draw solid conclusions regarding the efficacy of these agents.
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Maciejczyk, Mateusz, Anna Zalewska und Karolina Gerreth. „Salivary Redox Biomarkers in Selected Neurodegenerative Diseases“. Journal of Clinical Medicine 9, Nr. 2 (12.02.2020): 497. http://dx.doi.org/10.3390/jcm9020497.
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Neurodegenerative diseases (NDDs), such as Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease, are disorders, which cause irreversible and progressive deterioration of the central nervous system. The pathophysiology of NDDs is still not fully explained; nevertheless, oxidative stress is considered as a critical mediator of cerebral degeneration, brain inflammation, as well as neuronal apoptosis. Therefore, it is not surprising that redox biomarkers are increasingly used in the diagnosis of neurodegenerative diseases. As saliva is a very easy to obtain bioliquid, it seems promising to use this biomaterial in the diagnosis of NDDs. Saliva collection is easy, cheap, stress-free, and non-infectious, and it does not require the help of a specialised medical personnel. Additionally, the concentrations of many salivary redox biomarkers correlate with their content in blood serum as well as the degree of disease progression, which makes them non-invasive indicators of NDDs. This paper reviews the latest knowledge concerning the use of salivary redox biomarkers in the diagnosis and prognosis of selected neurodegenerative diseases.
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Gidikova, N., M. Sulowski, V. Petkov, R. Valov und G. Cempura. „Composite Coatings of Chromium and Nanodiamond Particles on Steel“. Archives of Metallurgy and Materials 62, Nr. 4 (01.12.2017): 2421–24. http://dx.doi.org/10.1515/amm-2017-0356.
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AbstractChrome plating is used to improve the properties of metal surfaces like hardness, corrosion resistance and wear resistance in machine building. To further improve these properties, an electrodeposited chromium coating on steel, modified with nanodiamond particles is proposed. The nanodiamond particles (average size 4 nm measured by TEM) are produced by detonation synthesis (NDDS). The composite coating (Cr+NDDS) has an increased thickness, about two times greater microhardness and finer micro-structure compared to that of unmodified chromium coating obtained under the same galvanization conditions. In the microstructure of specimen obtained from chrome electrolyte with concentration of NDDS 25 g/l or more, “minisections” with chromium shell were found. They were identified by metallographic microscope and X-ray analyser on etched section of chromium plated sample. The object of further research is the dependence of the presence of NDDS in the composite coating from the nanodiamond particles concentration in the chroming electrolyte.
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Lense, Miriam D., Eniko Ladányi, Tal-Chen Rabinowitch, Laurel Trainor und Reyna Gordon. „Rhythm and timing as vulnerabilities in neurodevelopmental disorders“. Philosophical Transactions of the Royal Society B: Biological Sciences 376, Nr. 1835 (23.08.2021): 20200327. http://dx.doi.org/10.1098/rstb.2020.0327.
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Millions of children are impacted by neurodevelopmental disorders (NDDs), which unfold early in life, have varying genetic etiologies and can involve a variety of specific or generalized impairments in social, cognitive and motor functioning requiring potentially lifelong specialized supports. While specific disorders vary in their domain of primary deficit (e.g. autism spectrum disorder (social), attention-deficit/hyperactivity disorder (attention), developmental coordination disorder (motor) and developmental language disorder (language)), comorbidities between NDDs are common. Intriguingly, many NDDs are associated with difficulties in skills related to rhythm, timing and synchrony though specific profiles of rhythm/timing impairments vary across disorders. Impairments in rhythm/timing may instantiate vulnerabilities for a variety of NDDs and may contribute to both the primary symptoms of each disorder as well as the high levels of comorbidities across disorders. Drawing upon genetic, neural, behavioural and interpersonal constructs across disorders, we consider how disrupted rhythm and timing skills early in life may contribute to atypical developmental cascades that involve overlapping symptoms within the context of a disorder's primary deficits. Consideration of the developmental context, as well as common and unique aspects of the phenotypes of different NDDs, will inform experimental designs to test this hypothesis including via potential mechanistic intervention approaches. This article is part of the theme issue ‘Synchrony and rhythm interaction: from the brain to behavioural ecology’.
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Zhang, Honglei, Yanjuan Wu, Xiao Xu, Chen Chen, Xiukun Xue, Ben Xu, Tianduo Li und Zhaowei Chen. „Synthesis Characterization of Platinum (IV) Complex Curcumin Backboned Polyprodrugs: In Vitro Drug Release Anticancer Activity“. Polymers 13, Nr. 1 (26.12.2020): 67. http://dx.doi.org/10.3390/polym13010067.
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The conventional mono-chemotherapy still suffers from unsatisfied potency for cancer therapy due to tumor heterogeneity and the occurrence of drug resistance. Combination chemotherapy based on the nanosized drug delivery systems (nDDSs) has been developed as a promising platform to circumvent the limitations of mono-chemotherapy. In this work, starting from cisplatin and curcumin (Cur), we prepared a dual drug backboned shattering polymeric nDDS for synergistic chemotherapy. By in situ polymerization of the Cur, platinum (IV) complex-based prodrug monomer (DHP), L-lysine diisocyanate (LDI), and then conjugation with a hydrophilic poly (ethylene glycol) monomethyl ether (mPEG) derivative, a backbone-type platinum (IV) and Cur linkage containing mPEG-poly(platinum-co-Cur)-mPEG (PCPt) copolymer was synthesized. Notably, the platinum (IV) (Pt (IV)) and Cur were incorporated into the hydrophobic segment of PCPt with the fixed drugs loading ratio and high drugs loading content. The batch-to-batch variability could be decreased. The resulting prodrug copolymer then self-assembled into nanoparticles (PCPt NPs) with an average diameter around 100 nm, to formulate a synergetic nDDS. Importantly, PCPt NPs could greatly improve the solubility and stability of Cur. In vitro drug release profiles have demonstrated that PCPt NPs were stable in PBS 7.4, rapid burst release was greatly decreased, and the Pt and Cur release could be largely enhanced under reductive conditions due to the complete dissociation of the hydrophobic main chain of PCPt. In vitro cell viability test indicated that PCPt NPs were efficient synergistic chemotherapy units. Moreover, PCPt NPs were synergistic for cisplatin-resistant cell lines A549/DDP cells, and they exhibited excellent reversal ability of tumor resistance to cisplatin. This work provides a promising strategy for the design and synthesis of nDDS for combination chemotherapy.
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Hafeez, Muhammad Nadeem, Christian Celia und Vilma Petrikaite. „Challenges towards Targeted Drug Delivery in Cancer Nanomedicines“. Processes 9, Nr. 9 (27.08.2021): 1527. http://dx.doi.org/10.3390/pr9091527.
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Despite cancer nanomedicine celebrates already thirty years since its introduction, together with the achievements and progress in cancer treatment area, it still undergoes serious disadvantages that must be addressed. Since the first observation that macromolecules tend to accumulate in tumor tissue due to fenestrated endothelial of vasculature, considered as the “royal gate” in drug delivery field, more than dozens of nanoformulations have been approved and introduced into the practice for cancer treatment. Lipid, polymeric, and hybrid nanocarriers are biocompatible nano-drug delivery systems (NDDs) having suitable physicochemical properties and modulate payload release in response to specific chemical or physical stimuli. Biopharmaceutical properties of NDDs and their efficacy in animal models and humans can significantly affect their impact and perspective in nanomedicine. One of the future directions could be focusing on personalized cancer treatment, considering the heterogeneity and complexity of each patient tumor tissue and the designing of multifunctional targeted NDDs combining synthetic nanomaterials and biological components, like cellular membranes, circulating proteins, RNAi/DNAi, which enforce the efficacy of NDDs and boost their therapeutic effect.
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Lee, Jieon, Diana Avramets, Byungsun Jeon und Hyunah Choo. „Modulation of Serotonin Receptors in Neurodevelopmental Disorders: Focus on 5-HT7 Receptor“. Molecules 26, Nr. 11 (02.06.2021): 3348. http://dx.doi.org/10.3390/molecules26113348.
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Since neurodevelopmental disorders (NDDs) influence more than 3% of children worldwide, there has been intense investigation to understand the etiology of disorders and develop treatments. Although there are drugs such as aripiprazole, risperidone, and lurasidone, these medications are not cures for the disorders and can only help people feel better or alleviate their symptoms. Thus, it is required to discover therapeutic targets in order to find the ultimate treatments of neurodevelopmental disorders. It is suggested that abnormal neuronal morphology in the neurodevelopment process is a main cause of NDDs, in which the serotonergic system is emerging as playing a crucial role. From this point of view, we noticed the correlation between serotonin receptor subtype 7 (5-HT7R) and NDDs including autism spectrum disorder (ASD), fragile X syndrome (FXS), and Rett syndrome (RTT). 5-HT7R modulators improved altered behaviors in animal models and also affected neuronal morphology via the 5-HT7R/G12 signaling pathway. Through the investigation of recent studies, it is suggested that 5-HT7R could be a potential therapeutic target for the treatment of NDDs.
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de Oliveira, Nayana Keyla Seabra, Marcos Rafael Silva Almeida, Franco Márcio Maciel Pontes, Mariana Pegrucci Barcelos, Carlos Henrique Tomich de Paula da Silva, Joaquín María Campos Rosa, Rodrigo Alves Soares Cruz und Lorane Izabel da Silva Hage-Melim. „Antioxidant Effect of Flavonoids Present in Euterpe oleracea Martius and Neurodegenerative Diseases: A Literature Review“. Central Nervous System Agents in Medicinal Chemistry 19, Nr. 2 (06.08.2019): 75–99. http://dx.doi.org/10.2174/1871524919666190502105855.
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Introduction:Neurodegenerative diseases (NDDs) are progressive, directly affecting the central nervous system (CNS), the most common and recurrent are Alzheimer's disease (AD) and Parkinson's disease (PD). One factor frequently mentioned in the etiology of NDDs is the generation of free radicals and oxidative stress, producing cellular damages. Studies have shown that the consumption of foods rich in polyphenols, especially those of the flavonoid class, has been related to the low risk in the development of several diseases. Due to the antioxidant properties present in the food, a fruit that has been gaining prominence among these foods is the Euterpe oleracea Mart. (açaí), because it presents in its composition significant amounts of a subclass of the flavonoids, the anthocyanins.Methods:In the case review, the authors receive a basic background on the most common NDDs, oxidative stress and antioxidants. In addition, revisiting the various studies related to NDDs, including flavonoids and consumption of açaí.Results:Detailed analysis of the recently reported case studies reveal that dietary consumption of flavonoid-rich foods, such as açaí fruits, suggests the efficacy to attenuate neurodegeneration and prevent or reverse the age-dependent deterioration of cognitive function.Conclusion:This systematic review points out that flavonoids presenting in açaí have the potential for the treatment of diseases such as PD and AD and are candidates for drugs in future clinical research. However, there is a need for in vitro and in vivo studies with polyphenol that prove and ratify the therapeutic potential of this fruit for several NDDs.
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Coomey, Rachel, Rianne Stowell, Ania Majewska und Daniela Tropea. „The Role of Microglia in Neurodevelopmental Disorders and their Therapeutics“. Current Topics in Medicinal Chemistry 20, Nr. 4 (27.03.2020): 272–76. http://dx.doi.org/10.2174/1568026620666200221172619.
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The development of new therapeutics is critically dependent on an understanding of the molecular pathways, the disruption of which results in neurological symptoms. Genetic and biomarker studies have highlighted immune signalling as a pathway that is impaired in patients with neurodevelopmental disorders (NDDs), and several studies on animal models of aberrant neurodevelopment have implicated microglia, the brain’s immune cells, in the pathology of these diseases. Despite the increasing awareness of the role of immune responses and inflammation in the pathophysiology of NDDs, the testing of new drugs rarely considers their effects in microglia. In this brief review, we present evidence of how the study of microglia can be critical for understanding the mechanisms of action of candidate drugs for NDDs and for increasing their therapeutic effect.
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Simioni, Andreza R., Marcelo M. M. Pelisson, Milton Beltrame und Antonio C. Tedesco. „Photophysical and Photobiological Studies of a Silicon Tribenzonaphthoporphyrazinato Incorporated into Liposomes for Photodynamic Therapy Use“. Journal of Nanoscience and Nanotechnology 8, Nr. 6 (01.06.2008): 3208–15. http://dx.doi.org/10.1166/jnn.2008.108.
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Nanostructured drug delivery systems (NDDS), such as liposomes, represent a growing area in biomedical research. These microheterogeneous media can be used in many biological systems to provide appropriate drug levels with a specific biodistribution. The photophysical properties of a silicon derivative of tribenzonaphthoporphyrazinato (Si-tri-PcNc) incorporated into liposome were studied by steady-state techniques, time-resolved fluorescence and laser flash photolysis. All the spectroscopy measurements performed allowed us to conclude that Si-tri-PcNc in liposome is a promising NDDS for PDT. The in vitro experiments with liposomal NDDS showed that the system is not cytotoxic in darkness, but exhibits a substantial phototoxicity at 1 μM of photosensitizer concentration and 10.0 J/cm2 of light. These conditions are sufficient to kill about 80% of the cells.
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Blanco-Martínez, Nerea, Laura Delgado-Lobete, Rebeca Montes-Montes, Nuria Ruiz-Pérez, Marcos Ruiz-Pérez und Sergio Santos-del-Riego. „Participation in Everyday Activities of Children with and without Neurodevelopmental Disorders: A Cross-Sectional Study in Spain“. Children 7, Nr. 10 (01.10.2020): 157. http://dx.doi.org/10.3390/children7100157.
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Children with neurodevelopmental disorders (NDDs) often report significant difficulties performing activities of daily living (ADLs), which may restrict their daily participation. The aim of this study was to investigate the differences in ADLs participation between children with NDDs and typically developing (TD) children, and to explore the associations between different daily participation contexts. A cross-sectional study was conducted that included twenty children with a medical diagnosis of an NDD and 26 sex- and age-matched TD controls. The daily participation across home, community, school, and instrumental living activities was measured using the Child and Adolescent Scale of Participation (CASP). The results show that children with NDDs engaged in lower participation in all CASP contexts (Δ = 1.7–5.5, p < 0.001) and had a significantly higher prevalence of moderate or severe restricted participation than their TD peers (OR = 23.4, 95% CI = 3.6–154.2, p < 0.001). Additionally, a strong association was found between the different contexts of participation (r = 0.642–0.856). Overall, the children with NDDs experienced significant participation restrictions on their daily activities. This study adds to the growing evidence showing that intervention strategies in this population should adopt a participation-oriented approach.
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Woolfenden, Sue, Kate Milner, Kali Tora, Kelera Naulumatua, Reapi Mataika, Fleur Smith, Raghu Lingam, Joseph Kado und Ilisapeci Tuibeqa. „Strengthening Health Systems to Support Children with Neurodevelopmental Disabilities in Fiji—A Commentary“. International Journal of Environmental Research and Public Health 17, Nr. 3 (04.02.2020): 972. http://dx.doi.org/10.3390/ijerph17030972.
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Supporting children with neurodevelopmental disabilities (NDDs) is recognized as an increasing priority in Fiji, a middle-income Pacific Island country. Our objective was to describe our approach to developing a model of care and strengthening local leadership in developmental paediatrics in Fiji to ensure high-quality identification, assessment and management of children with NDDs. Paediatric staff at Colonial War Memorial (CWM) Hospital in Suva have worked in partnership with Australian paediatricians to develop the model of care. The platform of continuing medical education during biannual 3 to 4 days of clinic-based teaching with visiting developmental paediatricians from Australia has been used. Since 2010, there have been 15 local and regional paediatric trainees trained. Since 2015, our two local lead paediatric trainees have run a weekly local developmental clinic. In total, 370 children aged 0 to 18 with NDDs have been comprehensively assessed with a detailed history and standardised tools. The model is extending to two divisional hospitals. Research engagement with the team is resulting in the development of a local evidence base. Local, regional and international leadership and collaboration has resulted in increased capacity in the Fijian health system to support children with NDDs.
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Liu, Kevin X., Roshan V. Sethi, Margaret B. Pulsifer, Alissa M. D’Gama, Beverly Lavally, Nancy J. Tarbell, Torunn I. Yock und Shannon M. MacDonald. „GCT-37. PREVALENCE OF AUTISM SPECTRUM DISORDER AND OTHER NEURODEVELOPMENTAL DISORDERS IN PEDIATRIC PATIENTS WITH INTRACRANIAL GERM CELL TUMORS“. Neuro-Oncology 22, Supplement_3 (01.12.2020): iii335. http://dx.doi.org/10.1093/neuonc/noaa222.256.
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Abstract PURPOSE/OBJECTIVE(s) Intracranial germ cell tumors (IGCTs) are rare tumors of the central nervous system with peak incidence around puberty. Due to the developmental origins of IGCTs, we investigated the prevalence of neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD), in our retrospective institutional cohort of patients diagnosed with IGCTs. MATERIALS/METHODS A retrospective review of medical records was conducted for 105 patients who were diagnosed with IGCTs and treated at Massachusetts General Hospital between 1998 and 2016. All patients with ASD had thorough neuropsychological assessment at the time of radiotherapy that confirmed their diagnoses. RESULTS Median age at diagnosis was 12.8 years (range: 4.3–21.6) and median follow-up time was 4.7 years (range: 0.4–15.8). Seventeen patients with IGCTs were diagnosed with NDDs prior to cancer diagnoses, including five patients with ASD, and three patients with chromosomal abnormalities, including one patient with Down syndrome. Interestingly, four of five patients with ASD developed pure germinomas, giving an ASD prevalence rate of 6.5% and 2.3% in the pure germinoma and NGGCT cohorts, respectively. All other patients had no known diagnoses of NDDs. CONCLUSIONS Our study found 17 patients with IGCTs were diagnosed with NDDs prior to their cancer diagnoses. An ASD prevalence of 6.5% in the pure germinoma cohort is more than three-fold greater than the national prevalence, suggesting there may be an association between ASD and pure germinomas. Future prospective studies with larger cohorts are still needed to examine associations between NDDs and ASD and IGCTs.
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Moreno-García, Leticia, Tresa López-Royo, Ana Cristina Calvo, Janne Markus Toivonen, Miriam de la Torre, Laura Moreno-Martínez, Nora Molina et al. „Competing Endogenous RNA Networks as Biomarkers in Neurodegenerative Diseases“. International Journal of Molecular Sciences 21, Nr. 24 (16.12.2020): 9582. http://dx.doi.org/10.3390/ijms21249582.
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Protein aggregation is classically considered the main cause of neuronal death in neurodegenerative diseases (NDDs). However, increasing evidence suggests that alteration of RNA metabolism is a key factor in the etiopathogenesis of these complex disorders. Non-coding RNAs are the major contributor to the human transcriptome and are particularly abundant in the central nervous system, where they have been proposed to be involved in the onset and development of NDDs. Interestingly, some ncRNAs (such as lncRNAs, circRNAs and pseudogenes) share a common functionality in their ability to regulate gene expression by modulating miRNAs in a phenomenon known as the competing endogenous RNA mechanism. Moreover, ncRNAs are found in body fluids where their presence and concentration could serve as potential non-invasive biomarkers of NDDs. In this review, we summarize the ceRNA networks described in Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis and spinocerebellar ataxia type 7, and discuss their potential as biomarkers of these NDDs. Although numerous studies have been carried out, further research is needed to validate these complex interactions between RNAs and the alterations in RNA editing that could provide specific ceRNET profiles for neurodegenerative disorders, paving the way to a better understanding of these diseases.
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Smirni, Daniela, Pietro Smirni, Marco Carotenuto, Lucia Parisi, Giuseppe Quatrosi und Michele Roccella. „Noli Me Tangere: Social Touch, Tactile Defensiveness, and Communication in Neurodevelopmental Disorders“. Brain Sciences 9, Nr. 12 (12.12.2019): 368. http://dx.doi.org/10.3390/brainsci9120368.
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Tactile defensiveness is a common feature in neurodevelopmental disorders (NDDs). Since the first studies, tactile defensiveness has been described as the result of an abnormal response to sensory stimulation. Moreover, it has been studied how the tactile system is closely linked to socio-communicative development and how the interoceptive sensory system supports both a discriminating touch and an affective touch. Therefore, several neurophysiological studies have been conducted to investigate the neurobiological basis of the development and functioning of the tactile system for a better understanding of the tactile defensiveness behavior and the social touch of NDDs. Given the lack of recent literature on tactile defensiveness, the current study provides a brief overview of the original contributions on this research topic in children with NDDs focusing attention on how this behavior has been considered over the years in the clinical setting.
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Nonweiler, Jacqueline, Fiona Rattray, Jennifer Baulcomb, Francesca Happé und Michael Absoud. „Prevalence and Associated Factors of Emotional and Behavioural Difficulties during COVID-19 Pandemic in Children with Neurodevelopmental Disorders“. Children 7, Nr. 9 (04.09.2020): 128. http://dx.doi.org/10.3390/children7090128.
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Children and young people (CYP) with neurodevelopmental disorders (NDDs) may be particularly vulnerable to adverse mental health effects due to the COVID-19 pandemic. We conducted a cross-sectional U.K. parent-reported study from 2nd April–2nd June 2020, using the Strengths and Difficulties Questionnaire. CYP with NDDs (n = 371), compared to neurotypical controls, had a higher prevalence of emotional symptoms (42% vs. 15%) and conduct problems (28% vs. 9%), and fewer prosocial behaviours (54% vs. 22%). All groups had worse emotional symptoms than pre-COVID groups, and those with attention-deficit/hyperactivity disorder showed inflated conduct problems, while those with autism spectrum disorder exhibited decreased prosocial behaviours. Females with ASD had higher emotional symptoms compared to males. CYP with NDDs, and those without, showed higher levels of parent-reported mental health problems than comparable cohorts pre-COVID-19.
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Fukutomi, Ryuuta, Tomokazu Ohishi, Yu Koyama, Monira Pervin, Yoriyuki Nakamura und Mamoru Isemura. „Beneficial Effects of Epigallocatechin-3-O-Gallate, Chlorogenic Acid, Resveratrol, and Curcumin on Neurodegenerative Diseases“. Molecules 26, Nr. 2 (14.01.2021): 415. http://dx.doi.org/10.3390/molecules26020415.
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Many observational and clinical studies have shown that consumption of diets rich in plant polyphenols have beneficial effects on various diseases such as cancer, obesity, diabetes, cardiovascular diseases, and neurodegenerative diseases (NDDs). Animal and cellular studies have indicated that these polyphenolic compounds contribute to such effects. The representative polyphenols are epigallocatechin-3-O-gallate in tea, chlorogenic acids in coffee, resveratrol in wine, and curcumin in curry. The results of human studies have suggested the beneficial effects of consumption of these foods on NDDs including Alzheimer’s and Parkinson’s diseases, and cellular animal experiments have provided molecular basis to indicate contribution of these representative polyphenols to these effects. This article provides updated information on the effects of these foods and their polyphenols on NDDs with discussions on mechanistic aspects of their actions mainly based on the findings derived from basic experiments.
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Luo, Fang, Aaron F. Sandhu, Wiramon Rungratanawanich, George E. Williams, Mohammed Akbar, Shuanhu Zhou, Byoung-Joon Song und Xin Wang. „Melatonin and Autophagy in Aging-Related Neurodegenerative Diseases“. International Journal of Molecular Sciences 21, Nr. 19 (28.09.2020): 7174. http://dx.doi.org/10.3390/ijms21197174.
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With aging, the nervous system gradually undergoes degeneration. Increased oxidative stress, endoplasmic reticulum stress, mitochondrial dysfunction, and cell death are considered to be common pathophysiological mechanisms of various neurodegenerative diseases (NDDs) such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), organophosphate-induced delayed neuropathy (OPIDN), and amyotrophic lateral sclerosis (ALS). Autophagy is a cellular basic metabolic process that degrades the aggregated or misfolded proteins and abnormal organelles in cells. The abnormal regulation of neuronal autophagy is accompanied by the accumulation and deposition of irregular proteins, leading to changes in neuron homeostasis and neurodegeneration. Autophagy exhibits both a protective mechanism and a damage pathway related to programmed cell death. Because of its “double-edged sword”, autophagy plays an important role in neurological damage and NDDs including AD, PD, HD, OPIDN, and ALS. Melatonin is a neuroendocrine hormone mainly synthesized in the pineal gland and exhibits a wide range of biological functions, such as sleep control, regulating circadian rhythm, immune enhancement, metabolism regulation, antioxidant, anti-aging, and anti-tumor effects. It can prevent cell death, reduce inflammation, block calcium channels, etc. In this review, we briefly discuss the neuroprotective role of melatonin against various NDDs via regulating autophagy, which could be a new field for future translational research and clinical studies to discover preventive or therapeutic agents for many NDDs.
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Trompetero, Adriana, Aldemar Gordillo, Mora Carolina del Pilar, Velasquillo María Cristina und Rosa Helena Bustos Cruz. „Alzheimer’s Disease and Parkinson’s Disease: A Review of Current Treatment Adopting a Nanotechnology Approach“. Current Pharmaceutical Design 24, Nr. 1 (22.03.2018): 22–45. http://dx.doi.org/10.2174/1381612823666170828133059.
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Neurodegenerative disorders (NDDs) are characterized by the progressive loss of structure or neuron function, often associated with neuronal death. Treatments for neurodegenerative diseases only address symptoms without having any disease-modifying effect but serious side effects. Currently, there is no effective treatment for NDDs. This is due to the poor flow of drugs to the blood-barrier brain (BBB) which does not allow macromolecules like proteins and peptides to pass through it. Targeted drug delivery to the central nervous system (CNS) for the diagnosis and treatment of NDDs, such as Alzheimer’s disease (AD), is restricted due to the limitations posed by the BBB as well as opsonization by plasma proteins in the systemic circulation and peripheral side-effects. Nanotechnology thereby presents a broad approach for transporting molecules through the BBB, thus allowing the entry of substances acting directly on the site affected by the disease. The aim of this review is to outline current strategies in nanotechnology for treating Alzheimer’s and Parkinson’s diseases.
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Nuzziello, Nicoletta, und Maria Liguori. „The MicroRNA Centrism in the Orchestration of Neuroinflammation in Neurodegenerative Diseases“. Cells 8, Nr. 10 (02.10.2019): 1193. http://dx.doi.org/10.3390/cells8101193.
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MicroRNAs (miRNAs) are small non-coding RNAs with a unique ability to regulate the transcriptomic profile by binding to complementary regulatory RNA sequences. The ability of miRNAs to enhance (proinflammatory miRNAs) or restrict (anti-inflammatory miRNAs) inflammatory signalling within the central nervous system is an area of ongoing research, particularly in the context of disorders that feature neuroinflammation, including neurodegenerative diseases (NDDs). Furthermore, the discovery of competing endogenous RNAs (ceRNAs) has led to an increase in the complexity of miRNA-mediated gene regulation, with a paradigm shift from a unidirectional to a bidirectional regulation, where miRNA acts as both a regulator and is regulated by ceRNAs. Increasing evidence has revealed that ceRNAs, including long non-coding RNAs, circular RNAs, and pseudogenes, can act as miRNA sponges to regulate neuroinflammation in NDDs within complex cross-talk regulatory machinery, which is referred to as ceRNA network (ceRNET). In this review, we discuss the role of miRNAs in neuroinflammatory regulation and the manner in which cellular and vesicular ceRNETs could influence neuroinflammatory dynamics in complex multifactorial diseases, such as NDDs.
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Mijanović, Olja, Ana Branković, Anton V. Borovjagin, Denis V. Butnaru, Evgeny A. Bezrukov, Roman B. Sukhanov, Anastasia Shpichka, Peter Timashev und Ilya Ulasov. „Battling Neurodegenerative Diseases with Adeno-Associated Virus-Based Approaches“. Viruses 12, Nr. 4 (18.04.2020): 460. http://dx.doi.org/10.3390/v12040460.
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Neurodegenerative diseases (NDDs) are most commonly found in adults and remain essentially incurable. Gene therapy using AAV vectors is a rapidly-growing field of experimental medicine that holds promise for the treatment of NDDs. To date, effective delivery of a therapeutic gene into target cells via AAV has been a major obstacle in the field. Ideally, transgenes should be delivered into the target cells specifically and efficiently, while promiscuous or off-target gene delivery should be minimized to avoid toxicity. In the pursuit of an ideal vehicle for NDD gene therapy, a broad variety of vector systems have been explored. Here we specifically outline the advantages of adeno-associated virus (AAV)-based vector systems for NDD therapy application. In contrast to many reviews on NDDs that can be found in the literature, this review is rather focused on AAV vector selection and their testing in experimental and preclinical NDD models. Preclinical and in vitro data reveal the strong potential of AAV for NDD-related diagnostics and therapeutic strategies.
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Bacci, Andrea, Massimiliano Runfola, Simona Sestito und Simona Rapposelli. „Beyond Antioxidant Effects: Nature-Based Templates Unveil New Strategies for Neurodegenerative Diseases“. Antioxidants 10, Nr. 3 (28.02.2021): 367. http://dx.doi.org/10.3390/antiox10030367.
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The complex network of malfunctioning pathways occurring in the pathogenesis of neurodegenerative diseases (NDDs) represents a huge hurdle in the development of new effective drugs to be used in therapy. In this context, redox reactions act as crucial regulators in the maintenance of neuronal microenvironment homeostasis. Particularly, their imbalance results in the severe compromising of organism’s natural defense systems and subsequently, in the instauration of deleterious OS, that plays a fundamental role in the insurgence and progress of NDDs. Despite the huge efforts in drug discovery programs, the identification process of new therapeutic agents able to counteract the relentless progress of neurodegenerative processes has produced low or no effective therapies. Consequently, a paradigm-shift in the drug discovery approach for these diseases is gradually occurring, paving the way for innovative therapeutical approaches, such as polypharmacology. The aim of this review is to provide an overview of the main pharmacological features of most promising nature-based scaffolds for a possible application in drug discovery, especially for NDDs, highlighting their multifaceted effects against OS and neuronal disorders.
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Lööf, E. „Additional challenges in children with idiopathic clubfoot: is it just the foot?“ Journal of Children's Orthopaedics 13, Nr. 3 (Juni 2019): 245–51. http://dx.doi.org/10.1302/1863-2548.13.190076.
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Purpose Treatment of idiopathic clubfoot (IC) has improved since the introduction of the Ponseti method. However, relapses are still common and primarily related to non-adherence to the brace regime. Our hypothesis was that IC might be more than just a structural deformity. Based on three studies, the aim of this paper was to provide an overview of findings regarding additional challenges within IC. Methods In total, 153 children with IC and 137 control children participated in the studies. The first study assessed gross motor skills in six motor tasks using the Clubfoot Assessment Protocol. The second and third studies surveyed neurodevelopmental difficulties (NDDs) using the Five to Fifteen (FTF) questionnaire and health-related quality of life (HRQoL) using the EuroQol-5D youth. Results A high percentage of gross motor deviations were found in children with IC compared with controls, and those correlated poorly with clubfoot severity and foot movement. Children with IC had a higher prevalence of NDDs on the FTF compared with the control group, including the domains: motor skills, perception and language. One-third of children with IC were defined as at risk of developmental disorders. In this subgroup, parents were less satisfied with the outcome of clubfoot treatment and the children reported worse HRQoL than those without NDDs. Conclusion The findings suggest additional challenges in children with IC, such as NDDs, apparently affecting both clubfoot treatment outcome and HRQoL. Thus, awareness of these challenges could be vital to further optimize treatment and support, for example, with regards to brace adherence. Level of Evidence II - Prognostic study
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Gidikova, N., A. Cias, V. Petkov, M. Madej, M. Sułowski und R. Valov. „Wear Resistant Chromium Coatings Modified with Diamond Nanoparticles/ Odporność Na Zużycie Ścierne Powłok Chromowych Modyfikowanych Nanocząstkami Diamentu“. Archives of Metallurgy and Materials 59, Nr. 4 (01.12.2014): 1513–16. http://dx.doi.org/10.2478/amm-2014-0257.
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Abstract Electrochemical chromium coatings on steel, modified with diamond nanoparticles (NDDS), were produced by detonation synthesis. Their particle size was from 10 to 50 nm. Galvanization conditions, current density, etc., concentration of NDDS, were studied in relation to the characteristics of the chromium coatings. The optimal conditions were determined to attain the maximal values of the physical and mechanical properties of the coating. Surface topography after wear testing was examined. Compared to unmodified chromium coating, microhardness of the surface increased to 1100 kg/mm2, wear resistance, expressed as % of mass loss, increased from 3 to 10 times.
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Sartor, Francesca, Jihan Anderson, Colin McCaig, Zosia Miedzybrodzka und Berndt Müller. „Mutation of genes controlling mRNA metabolism and protein synthesis predisposes to neurodevelopmental disorders“. Biochemical Society Transactions 43, Nr. 6 (27.11.2015): 1259–65. http://dx.doi.org/10.1042/bst20150168.
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Brain development is a tightly controlled process that depends upon differentiation and function of neurons to allow for the formation of functional neural networks. Mutation of genes encoding structural proteins is well recognized as causal for neurodevelopmental disorders (NDDs). Recent studies have shown that aberrant gene expression can also lead to disorders of neural development. Here we summarize recent evidence implicating in the aetiology of NDDs mutation of factors acting at the level of mRNA splicing, mRNA nuclear export, translation and mRNA degradation. This highlights the importance of these fundamental processes for human health and affords new strategies and targets for therapeutic intervention.
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Ma, Qingming, Jie Cao, Yang Gao, Shangcong Han, Yan Liang, Tingting Zhang, Xinyu Wang und Yong Sun. „Microfluidic-mediated nano-drug delivery systems: from fundamentals to fabrication for advanced therapeutic applications“. Nanoscale 12, Nr. 29 (2020): 15512–27. http://dx.doi.org/10.1039/d0nr02397c.
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Aldewachi, Hasan, Radhwan N. Al-Zidan, Matthew T. Conner und Mootaz M. Salman. „High-Throughput Screening Platforms in the Discovery of Novel Drugs for Neurodegenerative Diseases“. Bioengineering 8, Nr. 2 (23.02.2021): 30. http://dx.doi.org/10.3390/bioengineering8020030.
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Neurodegenerative diseases (NDDs) are incurable and debilitating conditions that result in progressive degeneration and/or death of nerve cells in the central nervous system (CNS). Identification of viable therapeutic targets and new treatments for CNS disorders and in particular, for NDDs is a major challenge in the field of drug discovery. These difficulties can be attributed to the diversity of cells involved, extreme complexity of the neural circuits, the limited capacity for tissue regeneration, and our incomplete understanding of the underlying pathological processes. Drug discovery is a complex and multidisciplinary process. The screening attrition rate in current drug discovery protocols mean that only one viable drug may arise from millions of screened compounds resulting in the need to improve discovery technologies and protocols to address the multiple causes of attrition. This has identified the need to screen larger libraries where the use of efficient high-throughput screening (HTS) becomes key in the discovery process. HTS can investigate hundreds of thousands of compounds per day. However, if fewer compounds could be screened without compromising the probability of success, the cost and time would be largely reduced. To that end, recent advances in computer-aided design, in silico libraries, and molecular docking software combined with the upscaling of cell-based platforms have evolved to improve screening efficiency with higher predictability and clinical applicability. We review, here, the increasing role of HTS in contemporary drug discovery processes, in particular for NDDs, and evaluate the criteria underlying its successful application. We also discuss the requirement of HTS for novel NDD therapies and examine the major current challenges in validating new drug targets and developing new treatments for NDDs.
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Gaikwad, Leena, und Sravani Lagala. „Prevalence and correlates of neurodevelopmental disorders among children in India: a narrative review“. International Journal of Contemporary Pediatrics 8, Nr. 1 (23.12.2020): 200. http://dx.doi.org/10.18203/2349-3291.ijcp20205438.
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Neurodevelopmental disorders (NDD) are seen disproportionately affecting the low-income communities. Paucity of consistent and large-scale studies in India and variations in assessment and diagnostic tools reduce the scope for generalization of prevalence estimates to national level. This review tried to consolidate the existing community-based evidence of the prevalence of NDDs, risk factors and comorbidities among children in India. We searched studies related to the review objectives on search engines PubMed and Google Scholar. The community or school-based studies in India, published in English language were included. The prevalence of each of these NDDs differed in different locations and age groups. The prevalence appeared to be increasing with increase in age. Non-institutional delivery, perinatal asphyxia or delayed crying, low birth weight or prematurity, neonatal illness or neurological infections were significantly associated with the NDDs. Most of the significant risk factors are modifiable with the help of effective programs to improve maternal and child healthcare and nutrition. Further large-scale, good-quality epidemiological studies in community settings are needed to develop and prioritize the delivery of the prevention and rehabilitation interventions.
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Lee, Davin, Min Gu Jo, Seung Yeon Kim, Chang Geon Chung und Sung Bae Lee. „Dietary Antioxidants and the Mitochondrial Quality Control: Their Potential Roles in Parkinson’s Disease Treatment“. Antioxidants 9, Nr. 11 (28.10.2020): 1056. http://dx.doi.org/10.3390/antiox9111056.
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Advances in medicine and dietary standards over recent decades have remarkably increased human life expectancy. Unfortunately, the chance of developing age-related diseases, including neurodegenerative diseases (NDDs), increases with increased life expectancy. High metabolic demands of neurons are met by mitochondria, damage of which is thought to contribute to the development of many NDDs including Parkinson’s disease (PD). Mitochondrial damage is closely associated with the abnormal production of reactive oxygen species (ROS), which are widely known to be toxic in various cellular environments, including NDD contexts. Thus, ways to prevent or slow mitochondrial dysfunction are needed for the treatment of these NDDs. In this review, we first detail how ROS are associated with mitochondrial dysfunction and review the cellular mechanisms, such as the mitochondrial quality control (MQC) system, by which neurons defend against both abnormal production of ROS and the subsequent accumulation of damaged mitochondria. We next highlight previous studies that link mitochondrial dysfunction with PD and how dietary antioxidants might provide reinforcement of the MQC system. Finally, we discuss how aging plays a role in mitochondrial dysfunction and PD before considering how healthy aging through proper diet and exercise may be salutary.
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Petrovic, Snjezana, Aleksandra Arsic, Danijela Ristic-Medic, Zorica Cvetkovic und Vesna Vucic. „Lipid Peroxidation and Antioxidant Supplementation in Neurodegenerative Diseases: A Review of Human Studies“. Antioxidants 9, Nr. 11 (13.11.2020): 1128. http://dx.doi.org/10.3390/antiox9111128.
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Being characterized by progressive and severe damage in neuronal cells, neurodegenerative diseases (NDDs) are the major cause of disability and morbidity in the elderly, imposing a significant economic and social burden. As major components of the central nervous system, lipids play important roles in neural health and pathology. Disturbed lipid metabolism, particularly lipid peroxidation (LPO), is associated with the development of many NDDs, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS), all of which show elevated levels of LPO products and LPO-modified proteins. Thus, the inhibition of neuronal oxidation might slow the progression and reduce the severity of NDD; natural antioxidants, such as polyphenols and antioxidant vitamins, seem to be the most promising agents. Here, we summarize current literature data that were derived from human studies on the effect of natural polyphenols and vitamins A, C, and E supplementation in patients with AD, PD, and ALS. Although these compounds may reduce the severity and slow the progression of NDD, research gaps remain in antioxidants supplementation in AD, PD, and ALS patients, which indicates that further human studies applying antioxidant supplementation in different forms of NDDs are urgently needed.
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da S. Hage-Melim, Lorane I., Jaderson V. Ferreira, Nayana K. S. de Oliveira, Lenir C. Correia, Marcos R. S. Almeida, João G. C. Poiani, Carlton A. Taft und Carlos H. T. de Paula da Silva. „The Impact of Natural Compounds on the Treatment of Neurodegenerative Diseases“. Current Organic Chemistry 23, Nr. 3 (09.05.2019): 335–60. http://dx.doi.org/10.2174/1385272823666190327100418.
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Neurodegenerative diseases (NDDs) are characterized by a progressive deterioration of the motor and/or cognitive function, that are often accompanied by psychiatric disorders, caused by a selective loss of neurons in the central nervous system. Among the NDDs we can mention Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS), spinocerebellar ataxia 3 (SCA3), spinal and bulbar muscular atrophy (SBMA) and Creutzfeldt-Jakob disease (CJD). AD and HD are characterized mainly by massive neuronal loss. PD, ALS, SCA3 and SBMA are agerelated diseases which have characteristic motor symptoms. CJD is an NDD caused by prion proteins. With increasing life expectancy, elderly populations tend to have more health problems, such as chronic diseases related to age and disability. Therefore, the development of therapeutic strategies to treat or prevent multiple pathophysiological conditions in the elderly can improve the expectation and quality of life. The attention of researchers has been focused on bioactive natural compounds that represent important resources in the discovery and development of drug candidates against NDDs. In this review, we discuss the pathogenesis, symptoms, potential targets, treatment and natural compounds effective in the treatment of AD, PD, HD, ALS, SCA3, SBMA and CJD.
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Vogel Ciernia, A., B. I. Laufer, H. Hwang, K. W. Dunaway, C. E. Mordaunt, R. L. Coulson, D. H. Yasui und J. M. LaSalle. „Epigenomic Convergence of Neural-Immune Risk Factors in Neurodevelopmental Disorder Cortex“. Cerebral Cortex 30, Nr. 2 (26.06.2019): 640–55. http://dx.doi.org/10.1093/cercor/bhz115.
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Abstract Neurodevelopmental disorders (NDDs) affect 7–14% of all children in developed countries and are one of the leading causes of lifelong disability. Epigenetic modifications are poised at the interface between genes and environment and are predicted to reveal insight into NDD etiology. Whole-genome bisulfite sequencing was used to examine DNA cytosine methylation in 49 human cortex samples from 3 different NDDs (autism spectrum disorder, Rett syndrome, and Dup15q syndrome) and matched controls. Integration of methylation changes across NDDs with relevant genomic and genetic datasets revealed differentially methylated regions (DMRs) unique to each type of NDD but with shared regulatory functions in neurons and microglia. NDD DMRs were enriched within promoter regions and for transcription factor binding sites with identified methylation sensitivity. DMRs from all 3 disorders were enriched for ontologies related to nervous system development and genes with disrupted expression in brain from neurodevelopmental or neuropsychiatric disorders. Genes associated with NDD DMRs showed expression patterns indicating an important role for altered microglial function during brain development. These findings demonstrate an NDD epigenomic signature in human cortex that will aid in defining therapeutic targets and early biomarkers at the interface of genetic and environmental NDD risk factors.
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Arim, Rubab G., Leanne C. Findlay und Dafna E. Kohen. „Participation in Physical Activity for Children with Neurodevelopmental Disorders“. International Journal of Pediatrics 2012 (2012): 1–9. http://dx.doi.org/10.1155/2012/460384.
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The purpose of this study was to compare rates of participation for children (4–9 years of age) with neurodevelopmental disorders (NDDs) with and without externalizing behavior problems (EBPs) with children without disability and to examine mediators of the relation between disability and physical activity participation. Data for this study were drawn from Cycle 7 (2006-07) of the Canadian National Longitudinal Survey of Children and Youth (NLSCY). The frequency of children’s participation in organized sports or physical activities varied depending on the child’s health condition with children with NDDs and both NDDs and EBPs participating least in organized sports or physical activities followed by children with EBPs only. In contrast, there were no statistically significant differences by health group for children’s participation in unorganized sports or physical activities. These differences remained even after controlling for the effects of other child and family sociodemographic characteristics, except for children with EBPs only. These findings highlight the importance of considering children’s primary and other existing health conditions as well as family sociodemographic characteristics in order to better understand the factors that influence participation in organized physical activities for children with disabilities.