Journal articles: 'Motoer Neuron Disease'

1

Genc, Baris, Oge Gozutok, Nuran Kocak, and P. Hande Ozdinler. "The Timing and Extent of Motor Neuron Vulnerability in ALS Correlates with Accumulation of Misfolded SOD1 Protein in the Cortex and in the Spinal Cord." Cells 9, no. 2 (February 22, 2020): 502. http://dx.doi.org/10.3390/cells9020502.

Full text

Abstract:

Understanding the cellular and molecular basis of selective vulnerability has been challenging, especially for motor neuron diseases. Developing drugs that improve the health of neurons that display selective vulnerability relies on in vivo cell-based models and quantitative readout measures that translate to patient outcome. We initially developed and characterized UCHL1-eGFP mice, in which motor neurons are labeled with eGFP that is stable and long-lasting. By crossing UCHL1-eGFP to amyotrophic lateral sclerosis (ALS) disease models, we generated ALS mouse models with fluorescently labeled motor neurons. Their examination over time began to reveal the cellular basis of selective vulnerability even within the related motor neuron pools. Accumulation of misfolded SOD1 protein both in the corticospinal and spinal motor neurons over time correlated with the timing and extent of degeneration. This further proved simultaneous degeneration of both upper and lower motor neurons, and the requirement to consider both upper and lower motor neuron populations in drug discovery efforts. Demonstration of the direct correlation between misfolded SOD1 accumulation and motor neuron degeneration in both cortex and spinal cord is important for building cell-based assays in vivo. Our report sets the stage for shifting focus from mice to diseased neurons for drug discovery efforts, especially for motor neuron diseases.

APA, Harvard, Vancouver, ISO, and other styles

2

Cork, Linda C. "Hereditary Canine Spinal Muscular Atrophy: An Animal Model of Motor Neuron Disease." Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques 18, S3 (August 1991): 432–34. http://dx.doi.org/10.1017/s0317167100032613.

Full text

Abstract:

ABSTRACT:Motor neuron diseases selectively produce degeneration and death of motor neurons; the pathogenesis of these disorders and the specificity for this population of neurons are unknown. Hereditary Canine Spinal Muscular Atrophy produces a lower motor neuron disease which is clinically and pathologically similar to human motor neuron disease: motor neurons dysfunction and degenerate. The canine model provides an opportunity to investigate early stages of disease when there are viable motor neurons still present and might be responsive to a variety of therapeutic interventions. The canine disease, like the human disease, is inherited as an autosomal dominant. The extensive canine pedigree of more than 200 characterized individuals permits genetic analysis using syntenic linkage techniques which may identify a marker for the canine trait and provide insights into homologous regions for study in human kindreds.

APA, Harvard, Vancouver, ISO, and other styles

3

Dr.U.J.JanI, Dr U. J. JanI, Dr Ashwin Patil, Dr Mitesh J. Makawana, Dr KalpeshH Patel, Dr Dignesh Vasava, and Dr TejasChaudhari Dr.TejasChaudhari. "Madras Variant Motor Neuron Disease - A Rare Presentation." International Journal of Scientific Research 3, no. 2 (June 1, 2012): 355–56. http://dx.doi.org/10.15373/22778179/feb2014/114.

Full text

APA, Harvard, Vancouver, ISO, and other styles

4

Souza, Paulo Victor Sgobbi de, Wladimir Bocca Vieira de Rezende Pinto, Flávio Moura Rezende Filho, and Acary Souza Bulle Oliveira. "Far beyond the motor neuron: the role of glial cells in amyotrophic lateral sclerosis." Arquivos de Neuro-Psiquiatria 74, no. 10 (October 2016): 849–54. http://dx.doi.org/10.1590/0004-282x20160117.

Full text

Abstract:

ABSTRACT Motor neuron disease is one of the major groups of neurodegenerative diseases, mainly represented by amyotrophic lateral sclerosis. Despite wide genetic and biochemical data regarding its pathophysiological mechanisms, motor neuron disease develops under a complex network of mechanisms not restricted to the unique functions of the alpha motor neurons but which actually involve diverse functions of glial cell interaction. This review aims to expose some of the leading roles of glial cells in the physiological mechanisms of neuron-glial cell interactions and the mechanisms related to motor neuron survival linked to glial cell functions.

APA, Harvard, Vancouver, ISO, and other styles

5

Shannon, P., D. Chitayat, K. Chong, C. Dunham, and C. Fallet-Bianco. "Motor neuron disease presenting with fetal akinesia." Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques 45, S1 (May 2018): S4. http://dx.doi.org/10.1017/cjn.2018.44.

Full text

Abstract:

By contrast to infantile spinal muscular atrophy, which usually links to deletions in the SMN genes, fetal onset motor neuron disease is poorly reported. We collected a series of twelve cases of fetal arthrogryposis (16-31 weeks gestational age) with fetal motor neuron disease and excluded infectious diseases, lysosomal storage disease and neuroaxonal dystrophy. Of these twelve, 3 were thought to be ischemic in nature with microvascular alterations and systemic or central nervous system ischemic injury. The remaining 9 all displayed marked reduction in anterior horn motor neurons. Of these 9, four demonstrated mineralised neurons, four demonstrated either neuronal loss or cavitation in the globus pallidus, and in two, degenerating neurons were detectable in the brainstem or globus pallidus. Specific sequencing of SMN1 was performed in 6 of 9 and was reported as normal. Whole exome sequencing was performed in 4 without definitive diagnosis. We conclude that fetal motor neuron disease can be distinguished from ischemic injury, is morphologically heterogeneous, may affect the globus pallidus and is rarely linked to SMN1 mutations.

APA, Harvard, Vancouver, ISO, and other styles

6

Karpe, Yashashree, Zhenyu Chen, and Xue-Jun Li. "Stem Cell Models and Gene Targeting for Human Motor Neuron Diseases." Pharmaceuticals 14, no. 6 (June 12, 2021): 565. http://dx.doi.org/10.3390/ph14060565.

Full text

Abstract:

Motor neurons are large projection neurons classified into upper and lower motor neurons responsible for controlling the movement of muscles. Degeneration of motor neurons results in progressive muscle weakness, which underlies several debilitating neurological disorders including amyotrophic lateral sclerosis (ALS), hereditary spastic paraplegias (HSP), and spinal muscular atrophy (SMA). With the development of induced pluripotent stem cell (iPSC) technology, human iPSCs can be derived from patients and further differentiated into motor neurons. Motor neuron disease models can also be generated by genetically modifying human pluripotent stem cells. The efficiency of gene targeting in human cells had been very low, but is greatly improved with recent gene editing technologies such as zinc-finger nucleases (ZFN), transcription activator-like effector nucleases (TALEN), and CRISPR-Cas9. The combination of human stem cell-based models and gene editing tools provides unique paradigms to dissect pathogenic mechanisms and to explore therapeutics for these devastating diseases. Owing to the critical role of several genes in the etiology of motor neuron diseases, targeted gene therapies have been developed, including antisense oligonucleotides, viral-based gene delivery, and in situ gene editing. This review summarizes recent advancements in these areas and discusses future challenges toward the development of transformative medicines for motor neuron diseases.

APA, Harvard, Vancouver, ISO, and other styles

7

Rubinowicz-Zasada, Maja, Aneta Orczyk, Marek Orczyk, and Jarosław Pasek. "Боковой амиотрофический склероз – болезнь двигательных нейронов. Клинический случай." Paediatrics & Family Medicine 2, no. 1 (March 31, 2015): 109–16. http://dx.doi.org/10.15557/pfm.2015.0011.

Full text

APA, Harvard, Vancouver, ISO, and other styles

8

Coppedè, Fabio. "An Overview of DNA Repair in Amyotrophic Lateral Sclerosis." Scientific World JOURNAL 11 (2011): 1679–91. http://dx.doi.org/10.1100/2011/853474.

Full text

Abstract:

Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND), is an adult onset neurodegenerative disorder characterised by the degeneration of cortical and spinal cord motor neurons, resulting in progressive muscular weakness and death. Increasing evidence supports mitochondrial dysfunction and oxidative DNA damage in ALS motor neurons. Several DNA repair enzymes are activated following DNA damage to restore genome integrity, and impairments in DNA repair capabilities could contribute to motor neuron degeneration. After a brief description of the evidence of DNA damage in ALS, this paper focuses on the available data on DNA repair activity in ALS neuronal tissue and disease animal models. Moreover, biochemical and genetic data on DNA repair in ALS are discussed in light of similar findings in other neurodegenerative diseases.

APA, Harvard, Vancouver, ISO, and other styles

9

Ozyurt, Tunch, and Mukesh Gautam. "Differential Epigenetic Signature of Corticospinal Motor Neurons in ALS." Brain Sciences 11, no. 6 (June 7, 2021): 754. http://dx.doi.org/10.3390/brainsci11060754.

Full text

Abstract:

Corticospinal motor neurons (CSMN) are an indispensable neuron population for the motor neuron circuitry. They are excitatory projection neurons, which collect information from different regions of the brain and transmit it to spinal cord targets, initiating and controlling motor function. CSMN degeneration is pronounced cellular event in motor neurons diseases, such as amyotrophic lateral sclerosis (ALS). Genetic mutations contribute to only about ten percent of ALS. Thus understanding the involvement of other factors, such as epigenetic controls, is immensely valuable. Here, we investigated epigenomic signature of CSMN that become diseased due to misfolded SOD1 toxicity and TDP-43 pathology, by performing quantitative analysis of 5-methylcytosine (5mC) and 5-hydroxymethycytosine (5hmC) expression profiles during end-stage of the disease in hSOD1G93A, and prpTDP-43A315T mice. Our analysis revealed that expression of 5mC was specifically reduced in CSMN of both hSOD1G93A and prpTDP-43A315T mice. However, 5hmC expression was increased in the CSMN that becomes diseased due to misfolded SOD1 and decreased in CSMN that degenerates due to TDP-43 pathology. These results suggest the presence of a distinct difference between different underlying causes. These differential epigenetic events might modulate the expression profiles of select genes, and ultimately contribute to the different paths that lead to CSMN vulnerability in ALS.

APA, Harvard, Vancouver, ISO, and other styles

10

Oh, Seong-il, Jin-Sung Park, Jung-Joon Sung, and Seung Hyun Kim. "Clinical Scales Used in Motor Neuron Disease." Journal of the Korean Neurological Association 39, no. 2 Suppl (May 1, 2021): 77–86. http://dx.doi.org/10.17340/jkna.2021.2.22.

Full text

Abstract:

Motor neuron diseases (MND) are heterogeneous spectra of disorders that that primarily affect the motor neurons (MN) resulting in motor nerve and muscle degeneration. The pathophysiological mechanisms of MN cell death are known to be combined with disturbance of proteostasis, ribonucleostasis and exaggerated neuro-inflammation. Amyotrophic lateral sclerosis is the prototypic disease of MND followed by spinal and bulbar muscular atrophy, spinal muscular atrophy, benign focal amyotrophy and other various diseases. Although diverse spectra of these diseases share common symptoms, significant differences are known in their clinical manifestations and their clinical progression. With increasing number of new clinical trials, the importance of selecting appropriate clinical scales for the monitoring of clinical progression in different types of MNDs should be emphasized. The purpose of this review is to illustrate different types of clinical scales and demonstrate how to utilize these in the clinical research field with consensus. With these efforts, we hope to be ready to understand different kinds of clinical scales in MND in participating global standard clinical trials.

APA, Harvard, Vancouver, ISO, and other styles

11

Winder, Toni R., and Roland N. Auer. "Sensory Neuron Degeneration in Familial Kugelberg-Welander Disease." Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques 16, no. 1 (February 1989): 67–70. http://dx.doi.org/10.1017/s0317167100028535.

Full text

Abstract:

ABSTRACT:A 53 year old man developed symptoms of motor neuron disease in childhood. There was a family history of a similar disorder and it was felt to represent a form of Kugelberg-Welander disease. In addition to the motor deficits, sensory abnormalities in his legs were documented during life. Autopsy revealed anterior horn cell loss throughout the length of the spinal cord, with preservation of the phrenic nucleus. The lumbar dorsal root ganglia showed active degeneration of sensory neurons, with nuclear changes exceeding cytoplasmic ones. The fasciculus gracilis showed Wallerian degeneration. The findings provide direct evidence that sensory neurons can degenerate in some forms of motor neuron disease, and that the “demyelination” or “degeneration” of posterior columns sometimes seen in the various forms of motor neuron disease may actually be secondary to cell body disease in the dorsal root ganglia.

APA, Harvard, Vancouver, ISO, and other styles

12

Lin, Yu-Lung, Yi-Wei Lin, Jennifer Nhieu, Xiaoyin Zhang, and Li-Na Wei. "Sonic Hedgehog-Gli1 Signaling and Cellular Retinoic Acid Binding Protein 1 Gene Regulation in Motor Neuron Differentiation and Diseases." International Journal of Molecular Sciences 21, no. 11 (June 9, 2020): 4125. http://dx.doi.org/10.3390/ijms21114125.

Full text

Abstract:

Cellular retinoic acid-binding protein 1 (CRABP1) is highly expressed in motor neurons. Degenerated motor neuron-like MN1 cells are engineered by introducing SODG93A or AR-65Q to model degenerated amyotrophic lateral sclerosis (ALS) or spinal bulbar muscular atrophy neurons. Retinoic acid (RA)/sonic hedgehog (Shh)-induced embryonic stem cells differentiation into motor neurons are employed to study up-regulation of Crabp1 by Shh. In SODG93A or AR-65Q MN1 neurons, CRABP1 level is reduced, revealing a correlation of motor neuron degeneration with Crabp1 down-regulation. Up-regulation of Crabp1 by Shh is mediated by glioma-associated oncogene homolog 1 (Gli1) that binds the Gli target sequence in Crabp1′s neuron-specific regulatory region upstream of minimal promoter. Gli1 binding triggers chromatin juxtaposition with minimal promoter, activating transcription. Motor neuron differentiation and Crabp1 up-regulation are both inhibited by blunting Shh with Gli inhibitor GANT61. Expression data mining of ALS and spinal muscular atrophy (SMA) motor neurons shows reduced CRABP1, coincided with reduction in Shh-Gli1 signaling components. This study reports motor neuron degeneration correlated with down-regulation in Crabp1 and Shh-Gli signaling. Shh-Gli up-regulation of Crabp1 involves specific chromatin remodeling. The physiological and pathological implication of this regulatory pathway in motor neuron degeneration is supported by gene expression data of ALS and SMA patients.

APA, Harvard, Vancouver, ISO, and other styles

13

Namazi, Mohammad Hasan, Isa Khaheshi, Habib Haybar, and Shooka Esmaeeli. "Cardiac Failure as an Unusual Presentation in a Patient with History of Amyotrophic Lateral Sclerosis." Case Reports in Neurological Medicine 2014 (2014): 1–3. http://dx.doi.org/10.1155/2014/986139.

Full text

Abstract:

Amyotrophic lateral sclerosis (ALS) is the most well-known form of motor neuron diseases in which both upper and lower motor neurons are involved in this disease. We presented an unusual case of ALS whom had presented with chief complaint of dyspnea. Cardiac failure was diagnosed at the final stage of the ALS disease. The pathogenetic mechanism leading to an elevated occurrence of cardiomyopathy in ALS is not comprehensible. Dilated cardiomyopathy has been explained in some previous studies. Based on the collected data, it was hypothesized that cardiomyopathy is underdiagnosed in the ALS population, probably because symptoms are masqueraded as a result of the patients’ disability. It was suggested that in all motor neuron diseases a serial cardiological evaluation should be executed, including annual echocardiography.

APA, Harvard, Vancouver, ISO, and other styles

14

Zhang, Shu-Zhen, Li-Xiang Ma, Wen-Jing Qian, Hong-Fu Li, Zhong-Feng Wang, Hong-Xia Wang, and Zhi-Ying Wu. "Modeling Neurological Disease by Rapid Conversion of Human Urine Cells into Functional Neurons." Stem Cells International 2016 (2016): 1–8. http://dx.doi.org/10.1155/2016/2452985.

Full text

Abstract:

Somatic cells can be directly converted into functional neurons by ectopic expression of defined factors and/or microRNAs. Since the first report of conversion mouse embryonic fibroblasts into functional neurons, the postnatal mouse, and human fibroblasts, astroglia, hepatocytes, and pericyte-derived cells have been converted into functional dopaminergic and motor neurons bothin vitroandin vivo. However, it is invasive to get all these materials. In the current study, we provide a noninvasive approach to obtain directly reprogrammed functional neurons by overexpression of the transcription factors Ascl1, Brn2, NeuroD, c-Myc, and Myt1l in human urine cells. These induced neuronal (iN) cells could express multiple neuron-specific proteins and generate action potentials. Moreover, urine cells from Wilson’s disease (WD) patient could also be directly converted into neurons. In conclusion, generation of iN cells from nonneural lineages is a feasible and befitting approach for neurological disease modeling.

APA, Harvard, Vancouver, ISO, and other styles

15

Reichenstein, Irit, Chen Eitan, Sandra Diaz-Garcia, Guy Haim, Iddo Magen, Aviad Siany, Mariah L. Hoye, et al. "Human genetics and neuropathology suggest a link between miR-218 and amyotrophic lateral sclerosis pathophysiology." Science Translational Medicine 11, no. 523 (December 18, 2019): eaav5264. http://dx.doi.org/10.1126/scitranslmed.aav5264.

Full text

Abstract:

Motor neuron–specific microRNA-218 (miR-218) has recently received attention because of its roles in mouse development. However, miR-218 relevance to human motor neuron disease was not yet explored. Here, we demonstrate by neuropathology that miR-218 is abundant in healthy human motor neurons. However, in amyotrophic lateral sclerosis (ALS) motor neurons, miR-218 is down-regulated and its mRNA targets are reciprocally up-regulated (derepressed). We further identify the potassium channel Kv10.1 as a new miR-218 direct target that controls neuronal activity. In addition, we screened thousands of ALS genomes and identified six rare variants in the human miR-218-2 sequence. miR-218 gene variants fail to regulate neuron activity, suggesting the importance of this small endogenous RNA for neuronal robustness. The underlying mechanisms involve inhibition of miR-218 biogenesis and reduced processing by DICER. Therefore, miR-218 activity in motor neurons may be susceptible to failure in human ALS, suggesting that miR-218 may be a potential therapeutic target in motor neuron disease.

APA, Harvard, Vancouver, ISO, and other styles

16

Williams, U. E., E. E. Philip-Ephraim, and S. K. Oparah. "Multidisciplinary Interventions in Motor Neuron Disease." Journal of Neurodegenerative Diseases 2014 (November 18, 2014): 1–10. http://dx.doi.org/10.1155/2014/435164.

Full text

Abstract:

Motor neuron disease is a neurodegenerative disease characterized by loss of upper motor neuron in the motor cortex and lower motor neurons in the brain stem and spinal cord. Death occurs 2–4 years after the onset of the disease. A complex interplay of cellular processes such as mitochondrial dysfunction, oxidative stress, excitotoxicity, and impaired axonal transport are proposed pathogenetic processes underlying neuronal cell loss. Currently evidence exists for the use of riluzole as a disease modifying drug; multidisciplinary team care approach to patient management; noninvasive ventilation for respiratory management; botulinum toxin B for sialorrhoea treatment; palliative care throughout the course of the disease; and Modafinil use for fatigue treatment. Further research is needed in management of dysphagia, bronchial secretion, pseudobulbar affect, spasticity, cramps, insomnia, cognitive impairment, and communication in motor neuron disease.

APA, Harvard, Vancouver, ISO, and other styles

17

Zhao, Jing, Claire H. Stevens, Andrew W. Boyd, Lezanne Ooi, and Perry F. Bartlett. "Role of EphA4 in Mediating Motor Neuron Death in MND." International Journal of Molecular Sciences 22, no. 17 (August 30, 2021): 9430. http://dx.doi.org/10.3390/ijms22179430.

Full text

Abstract:

Motor neuron disease (MND) comprises a group of fatal neurodegenerative diseases with no effective cure. As progressive motor neuron cell death is one of pathological characteristics of MND, molecules which protect these cells are attractive therapeutic targets. Accumulating evidence indicates that EphA4 activation is involved in MND pathogenesis, and inhibition of EphA4 improves functional outcomes. However, the underlying mechanism of EphA4’s function in MND is unclear. In this review, we first present results to demonstrate that EphA4 signalling acts directly on motor neurons to cause cell death. We then review the three most likely mechanisms underlying this effect.

APA, Harvard, Vancouver, ISO, and other styles

18

Shell, L. G., B. S. Jortner, and M. S. Leib. "Familial Motor Neuron Disease in Rottweiler Dogs: Neuropathologic Studies." Veterinary Pathology 24, no. 2 (March 1987): 135–39. http://dx.doi.org/10.1177/030098588702400206.

Full text

Abstract:

Two 6-week-old female Rottweiler littermates were evaluated for regurgitation, diminished growth, progressive ataxia, and pelvic limb weakness. Clinical examination indicated a progressive, diffuse, lower motor neuron disorder and megaesophagus. The pups were killed at 6 and 8 weeks of age. Lesions included central chromatolysis and swelling of the perikarya in many large motor neurons in the ventral gray matter of the spinal cord. Some involvement of red, oculomotor, trigeminal motor, and ambiguus nuclei of the brainstem was noted. Ultrastructurally, chromatolytic neurons had excess neurofilaments, and an increase in and enlargement of Golgi complexes. Wallerian-like degeneration was prominent in neuropil of spinal cord and in peripheral nerve. Clinical, histological, and ultrastructural findings were consistent with a progressive motor neuron disease.

APA, Harvard, Vancouver, ISO, and other styles

19

Scaricamazza, Silvia, Illari Salvatori, Alberto Ferri, and Cristiana Valle. "Skeletal Muscle in ALS: An Unappreciated Therapeutic Opportunity?" Cells 10, no. 3 (March 2, 2021): 525. http://dx.doi.org/10.3390/cells10030525.

Full text

Abstract:

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the selective degeneration of upper and lower motor neurons and by the progressive weakness and paralysis of voluntary muscles. Despite intense research efforts and numerous clinical trials, it is still an incurable disease. ALS had long been considered a pure motor neuron disease; however, recent studies have shown that motor neuron protection is not sufficient to prevent the course of the disease since the dismantlement of neuromuscular junctions occurs before motor neuron degeneration. Skeletal muscle alterations have been described in the early stages of the disease, and they seem to be mainly involved in the “dying back” phenomenon of motor neurons and metabolic dysfunctions. In recent years, skeletal muscles have been considered crucial not only for the etiology of ALS but also for its treatment. Here, we review clinical and preclinical studies that targeted skeletal muscles and discuss the different approaches, including pharmacological interventions, supplements or diets, genetic modifications, and training programs.

APA, Harvard, Vancouver, ISO, and other styles

20

Wyatt, Tanya J., Sharyn L. Rossi, Monica M. Siegenthaler, Jennifer Frame, Rockelle Robles, Gabriel Nistor, and Hans S. Keirstead. "Human Motor Neuron Progenitor Transplantation Leads to Endogenous Neuronal Sparing in 3 Models of Motor Neuron Loss." Stem Cells International 2011 (2011): 1–11. http://dx.doi.org/10.4061/2011/207230.

Full text

Abstract:

Motor neuron loss is characteristic of many neurodegenerative disorders and results in rapid loss of muscle control, paralysis, and eventual death in severe cases. In order to investigate the neurotrophic effects of a motor neuron lineage graft, we transplanted human embryonic stem cell-derived motor neuron progenitors (hMNPs) and examined their histopathological effect in three animal models of motor neuron loss. Specifically, we transplanted hMNPs into rodent models of SMA (Δ7SMN), ALS (SOD1 G93A), and spinal cord injury (SCI). The transplanted cells survived and differentiated in all models. In addition, we have also found that hMNPs secrete physiologically active growth factorsin vivo, including NGF and NT-3, which significantly enhanced the number of spared endogenous neurons in all three animal models. The ability to maintain dying motor neurons by delivering motor neuron-specific neurotrophic support represents a powerful treatment strategy for diseases characterized by motor neuron loss.

APA, Harvard, Vancouver, ISO, and other styles

21

Clark, Courtney M., Rosemary M. Clark, Joshua A. Hoyle, Jyoti A. Chuckowree, Catriona A. McLean, and Tracey C. Dickson. "Differential NPY-Y1 Receptor Density in the Motor Cortex of ALS Patients and Familial Model of ALS." Brain Sciences 11, no. 8 (July 23, 2021): 969. http://dx.doi.org/10.3390/brainsci11080969.

Full text

Abstract:

Destabilization of faciliatory and inhibitory circuits is an important feature of corticomotor pathology in amyotrophic lateral sclerosis (ALS). While GABAergic inputs to upper motor neurons are reduced in models of the disease, less understood is the involvement of peptidergic inputs to upper motor neurons in ALS. The neuropeptide Y (NPY) system has been shown to confer neuroprotection against numerous pathogenic mechanisms implicated in ALS. However, little is known about how the NPY system functions in the motor system. Herein, we investigate post-synaptic NPY signaling on upper motor neurons in the rodent and human motor cortex, and on cortical neuron populations in vitro. Using immunohistochemistry, we show the increased density of NPY-Y1 receptors on the soma of SMI32-positive upper motor neurons in post-mortem ALS cases and SOD1G93A excitatory cortical neurons in vitro. Analysis of receptor density on Thy1-YFP-H-positive upper motor neurons in wild-type and SOD1G93A mouse tissue revealed that the distribution of NPY-Y1 receptors was changed on the apical processes at early-symptomatic and late-symptomatic disease stages. Together, our data demonstrate the differential density of NPY-Y1 receptors on upper motor neurons in a familial model of ALS and in ALS cases, indicating a novel pathway that may be targeted to modulate upper motor neuron activity.

APA, Harvard, Vancouver, ISO, and other styles

22

Kaifer, Kevin A., Eric Villalón, Benjamin S. O'Brien, Samantha L. Sison, Caley E. Smith, Madeline E. Simon, Jose Marquez, et al. "AAV9-mediated delivery of miR-23a reduces disease severity in Smn2B/−SMA model mice." Human Molecular Genetics 28, no. 19 (May 20, 2019): 3199–210. http://dx.doi.org/10.1093/hmg/ddz142.

Full text

Abstract:

Abstract Spinal muscular atrophy (SMA) is a neuromuscular disease caused by deletions or mutations in survival motor neuron 1 (SMN1). The molecular mechanisms underlying motor neuron degeneration in SMA remain elusive, as global cellular dysfunction obscures the identification and characterization of disease-relevant pathways and potential therapeutic targets. Recent reports have implicated microRNA (miRNA) dysregulation as a potential contributor to the pathological mechanism in SMA. To characterize miRNAs that are differentially regulated in SMA, we profiled miRNA levels in SMA induced pluripotent stem cell (iPSC)-derived motor neurons. From this array, miR-23a downregulation was identified selectively in SMA motor neurons, consistent with previous reports where miR-23a functioned in neuroprotective and muscle atrophy-antagonizing roles. Reintroduction of miR-23a expression in SMA patient iPSC-derived motor neurons protected against degeneration, suggesting a potential miR-23a-specific disease-modifying effect. To assess this activity in vivo, miR-23a was expressed using a self-complementary adeno-associated virus serotype 9 (scAAV9) viral vector in the Smn2B/− SMA mouse model. scAAV9-miR-23a significantly reduced the pathology in SMA mice, including increased motor neuron size, reduced neuromuscular junction pathology, increased muscle fiber area, and extended survival. These experiments demonstrate that miR-23a is a novel protective modifier of SMA, warranting further characterization of miRNA dysfunction in SMA.

APA, Harvard, Vancouver, ISO, and other styles

23

Rich, Mark M., Robert F. Waldeck, Linda C. Cork, Rita J. Balice-Gordon, Robert E. W. Fyffe, Xueyong Wang, Timothy C. Cope, and Martin J. Pinter. "Reduced Endplate Currents Underlie Motor Unit Dysfunction in Canine Motor Neuron Disease." Journal of Neurophysiology 88, no. 6 (December 1, 2002): 3293–304. http://dx.doi.org/10.1152/jn.00270.2002.

Full text

Abstract:

Hereditary canine spinal muscular atrophy (HCSMA) is an autosomal dominant degenerative disorder of motor neurons. In homozygous animals, motor units produce decreased force output and fail during repetitive activity. Previous studies suggest that decreased efficacy of neuromuscular transmission underlies these abnormalities. To examine this, we recorded muscle fiber endplate currents (EPCs) and found reduced amplitudes and increased failures during nerve stimulation in homozygotes compared with wild-type controls. Comparison of EPC amplitudes with muscle fiber current thresholds indicate that many EPCs from homozygotes fall below threshold for activating muscle fibers but can be raised above threshold following potentiation. To determine whether axonal abnormalities might play a role in causing motor unit dysfunction, we examined the postnatal maturation of axonal conduction velocity in relation to the appearance of tetanic failure. We also examined intracellularly labeled motor neurons for evidence of axonal neurofilament accumulations, which are found in many instances of motor neuron disease including HCSMA. Despite the appearance of tetanic failure between 90 and 120 days, average motor axon conduction velocity increased with age in homozygotes and achieved adult levels. Normal correlations between motor neuron properties (including conduction velocity) and motor unit properties were also observed. Labeled proximal motor axons of several motor neurons that supplied failing motor units exhibited little or no evidence of axonal swellings. We conclude that decreased release of transmitter from motor terminals underlies motor unit dysfunction in HCSMA and that the mechanisms determining the maturation of axonal conduction velocity and the pattern of correlation between motor neuron and motor unit properties do not contribute to the appearance or evolution of motor unit dysfunction.

APA, Harvard, Vancouver, ISO, and other styles

24

Bax, Monique, Jessie McKenna, Dzung Do-Ha, Claire H. Stevens, Sarah Higginbottom, Rachelle Balez, Mauricio e. Castro Cabral-da-Silva, et al. "The Ubiquitin Proteasome System Is a Key Regulator of Pluripotent Stem Cell Survival and Motor Neuron Differentiation." Cells 8, no. 6 (June 13, 2019): 581. http://dx.doi.org/10.3390/cells8060581.

Full text

Abstract:

The ubiquitin proteasome system (UPS) plays an important role in regulating numerous cellular processes, and a dysfunctional UPS is thought to contribute to motor neuron disease. Consequently, we sought to map the changing ubiquitome in human iPSCs during their pluripotent stage and following differentiation to motor neurons. Ubiquitinomics analysis identified that spliceosomal and ribosomal proteins were more ubiquitylated in pluripotent stem cells, whilst proteins involved in fatty acid metabolism and the cytoskeleton were specifically ubiquitylated in the motor neurons. The UPS regulator, ubiquitin-like modifier activating enzyme 1 (UBA1), was increased 36-fold in the ubiquitome of motor neurons compared to pluripotent stem cells. Thus, we further investigated the functional consequences of inhibiting the UPS and UBA1 on motor neurons. The proteasome inhibitor MG132, or the UBA1-specific inhibitor PYR41, significantly decreased the viability of motor neurons. Consistent with a role of the UPS in maintaining the cytoskeleton and regulating motor neuron differentiation, UBA1 inhibition also reduced neurite length. Pluripotent stem cells were extremely sensitive to MG132, showing toxicity at nanomolar concentrations. The motor neurons were more resilient to MG132 than pluripotent stem cells but demonstrated higher sensitivity than fibroblasts. Together, this data highlights the important regulatory role of the UPS in pluripotent stem cell survival and motor neuron differentiation.

APA, Harvard, Vancouver, ISO, and other styles

25

Carrasco, Dario I., Mark M. Rich, Qingbo Wang, Timothy C. Cope, and Martin J. Pinter. "Activity-Driven Synaptic and Axonal Degeneration in Canine Motor Neuron Disease." Journal of Neurophysiology 92, no. 2 (August 2004): 1175–81. http://dx.doi.org/10.1152/jn.00157.2004.

Full text

Abstract:

The role of neuronal activity in the pathogenesis of neurodegenerative disease is largely unknown. In this study, we examined the effects of increasing motor neuron activity on the pathogenesis of a canine version of inherited motor neuron disease (hereditary canine spinal muscular atrophy). Activity of motor neurons innervating the ankle extensor muscle medial gastrocnemius (MG) was increased by denervating close synergist muscles. In affected animals, 4 wk of synergist denervation accelerated loss of motor-unit function relative to control muscles and decreased motor axon conduction velocities. Slowing of axon conduction was greatest in the most distal portions of motor axons. Morphological analysis of neuromuscular junctions (NMJs) showed that these functional changes were associated with increased loss of intact innervation and with the appearance of significant motor axon and motor terminal sprouting. These effects were not observed in the MG muscles of age-matched, normal animals with synergist denervation for 5 wk. The results indicate that motor neuron action potential activity is a major contributing factor to the loss of motor-unit function and degeneration in inherited canine motor neuron disease.

APA, Harvard, Vancouver, ISO, and other styles

26

Wokke, JohnH J. "Diseases that masquerade as motor neuron disease." Lancet 347, no. 9012 (May 1996): 1347–48. http://dx.doi.org/10.1016/s0140-6736(96)91005-3.

Full text

APA, Harvard, Vancouver, ISO, and other styles

27

Genc, Baris, Oge Gozutok, and P. Hande Ozdinler. "Complexity of Generating Mouse Models to Study the Upper Motor Neurons: Let Us Shift Focus from Mice to Neurons." International Journal of Molecular Sciences 20, no. 16 (August 7, 2019): 3848. http://dx.doi.org/10.3390/ijms20163848.

Full text

Abstract:

Motor neuron circuitry is one of the most elaborate circuitries in our body, which ensures voluntary and skilled movement that requires cognitive input. Therefore, both the cortex and the spinal cord are involved. The cortex has special importance for motor neuron diseases, in which initiation and modulation of voluntary movement is affected. Amyotrophic lateral sclerosis (ALS) is defined by the progressive degeneration of both the upper and lower motor neurons, whereas hereditary spastic paraplegia (HSP) and primary lateral sclerosis (PLS) are characterized mainly by the loss of upper motor neurons. In an effort to reveal the cellular and molecular basis of neuronal degeneration, numerous model systems are generated, and mouse models are no exception. However, there are many different levels of complexities that need to be considered when developing mouse models. Here, we focus our attention to the upper motor neurons, which are one of the most challenging neuron populations to study. Since mice and human differ greatly at a species level, but the cells/neurons in mice and human share many common aspects of cell biology, we offer a solution by focusing our attention to the affected neurons to reveal the complexities of diseases at a cellular level and to improve translational efforts.

APA, Harvard, Vancouver, ISO, and other styles

28

Lindsay, Ronald M. "Trophic protection of motor neurons: clinical potential in motor neuron diseases." Journal of Neurology 242, S1 (1994): S8—S11. http://dx.doi.org/10.1007/bf00939232.

Full text

APA, Harvard, Vancouver, ISO, and other styles

29

Le, Nhat T. T., Lydia Chang, Irina Kovlyagina, Polymnia Georgiou, Nathaniel Safren, Kerstin E. Braunstein, Mark D. Kvarta, et al. "Motor neuron disease, TDP-43 pathology, and memory deficits in mice expressing ALS–FTD-linked UBQLN2 mutations." Proceedings of the National Academy of Sciences 113, no. 47 (November 9, 2016): E7580—E7589. http://dx.doi.org/10.1073/pnas.1608432113.

Full text

Abstract:

Missense mutations in ubiquilin 2 (UBQLN2) cause ALS with frontotemporal dementia (ALS–FTD). Animal models of ALS are useful for understanding the mechanisms of pathogenesis and for preclinical investigations. However, previous rodent models carrying UBQLN2 mutations failed to manifest any sign of motor neuron disease. Here, we show that lines of mice expressing either the ALS–FTD-linked P497S or P506T UBQLN2 mutations have cognitive deficits, shortened lifespans, and develop motor neuron disease, mimicking the human disease. Neuropathologic analysis of the mice with end-stage disease revealed the accumulation of ubiquitinated inclusions in the brain and spinal cord, astrocytosis, a reduction in the number of hippocampal neurons, and reduced staining of TAR-DNA binding protein 43 in the nucleus, with concomitant formation of ubiquitin+ inclusions in the cytoplasm of spinal motor neurons. Moreover, both lines displayed denervation muscle atrophy and age-dependent loss of motor neurons that correlated with a reduction in the number of large-caliber axons. By contrast, two mouse lines expressing WT UBQLN2 were mostly devoid of clinical and pathological signs of disease. These UBQLN2 mouse models provide valuable tools for identifying the mechanisms underlying ALS–FTD pathogenesis and for investigating therapeutic strategies to halt disease.

APA, Harvard, Vancouver, ISO, and other styles

30

Villalón, E., R. A. Kline, C. E. Smith, Z. C. Lorson, E. Y. Osman, S. O’Day, L. M. Murray, and C. L. Lorson. "AAV9-Stathmin1 gene delivery improves disease phenotype in an intermediate mouse model of spinal muscular atrophy." Human Molecular Genetics 28, no. 22 (July 31, 2019): 3742–54. http://dx.doi.org/10.1093/hmg/ddz188.

Full text

Abstract:

Abstract Spinal muscular atrophy (SMA) is a devastating infantile genetic disorder caused by the loss of survival motor neuron (SMN) protein that leads to premature death due to loss of motor neurons and muscle atrophy. The approval of an antisense oligonucleotide therapy for SMA was an important milestone in SMA research; however, effective next-generation therapeutics will likely require combinatorial SMN-dependent therapeutics and SMN-independent disease modifiers. A recent cross-disease transcriptomic analysis identified Stathmin-1 (STMN1), a tubulin-depolymerizing protein, as a potential disease modifier across different motor neuron diseases, including SMA. Here, we investigated whether viral-based delivery of STMN1 decreased disease severity in a well-characterized SMA mouse model. Intracerebroventricular delivery of scAAV9-STMN1 in SMA mice at P2 significantly increased survival and weight gain compared to untreated SMA mice without elevating Smn levels. scAAV9-STMN1 improved important hallmarks of disease, including motor function, NMJ pathology and motor neuron cell preservation. Furthermore, scAAV9-STMN1 treatment restored microtubule networks and tubulin expression without affecting tubulin stability. Our results show that scAAV9-STMN1 treatment improves SMA pathology possibly by increasing microtubule turnover leading to restored levels of stable microtubules. Overall, these data demonstrate that STMN1 can significantly reduce the SMA phenotype independent of restoring SMN protein and highlight the importance of developing SMN-independent therapeutics for the treatment of SMA.

APA, Harvard, Vancouver, ISO, and other styles

31

Zgórzyńska, Emilia, Klaudia Krawczyk, Patrycja Bełdzińska, and Anna Walczewska. "Molecular basis of proteinopathies: Etiopathology of dementia and motor disorders." Postępy Higieny i Medycyny Doświadczalnej 75 (June 18, 2021): 456–73. http://dx.doi.org/10.5604/01.3001.0014.9513.

Full text

Abstract:

Neurodegenerative diseases are one of the most important medical and social problems affecting elderly people, the percentage of which is significantly increasing in the total world population. The cause of these diseases is the destruction of neurons by protein aggregates that form pathological deposits in neurons, glial cells and in the intercellular space. Proteins whose molecules are easily destabilized by point mutations or endogenous processes are alpha-synuclein (ASN), tau and TDP-43. Pathological forms of these proteins form characteristic aggregates, which accumulate in the neurons and are the cause of various forms of dementia and motor disorders. The most common causes of dementia are tauopathies. In primary tauopathies, which include progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), Pick’s disease (PiD), and frontotemporal dementia (FTD), modified tau molecules disrupt axonal transport and protein distribution in neurons. Ultimately, the helical filaments and neurofibrillary tangles of tau lead to neuron death in various structures of the brain. In Alzheimer’s disease hyperphosphorylated tau tangles along with β amyloid plaques are responsible for the degeneration of the hippocampus, entorhinal cortex and amygdala. The most prevalent synucleinopathies are Parkinson’s disease, multiple system atrophy (MSA) and dementia with Lewy bodies, where there is a degeneration of neurons in the extrapyramidal tracts or, as in MSA, autonomic nerves. TDP-43 inclusions in the cytoplasm cause the degeneration of motor neurons in amyotrophic lateral sclerosis (ALS) and in one of the frontotemporal dementia variant (FTLD-TDP). In this work ASN, tau and TDP-43 structures are described, as well as the genetic and sporadic factors that lead to the destabilization of molecules, their aggregation and incorrect distribution in neurons, which are the causes of neurodegenerative diseases.

APA, Harvard, Vancouver, ISO, and other styles

32

Strayer, Amy L., Cassandra N. Dennys-Rivers, Karina C. Ricart, Narae Bae, Joseph S. Beckman, Maria Clara Franco, and Alvaro G. Estevez. "Ligand-independent activation of the P2X7 receptor by Hsp90 inhibition stimulates motor neuron apoptosis." Experimental Biology and Medicine 244, no. 11 (May 29, 2019): 901–14. http://dx.doi.org/10.1177/1535370219853798.

Full text

Abstract:

Activation of the extracellular ATP ionotropic receptor P2X7 stimulates motor neuron apoptosis, whereas its inhibition in cell and animal models of amyotrophic lateral sclerosis can be protective. These observations suggest that P2X7 receptor activation is relevant to motor neuron disease and that it could be targeted for therapeutic development. Heat shock protein 90 (Hsp90) is an integral regulatory component of the P2X7 receptor complex, antagonizing ligand-induced receptor activation. Here, we show that the repressive activity of Hsp90 on P2X7 receptor activation in primary motor neurons is highly sensitive to inhibition. Primary motor neurons in culture are 100-fold more sensitive to Hsp90 inhibition by geldanamycin than other neuronal populations. Pharmacological inhibition and down-regulation of the P2X7 receptor prevented motor neuron apoptosis triggered by Hsp90 inhibition, which occurred in the absence of extracellular ATP. These observations suggest that inhibition of a seemingly motor neuron specific pool of Hsp90 leads to ligand independent activation of P2X7 receptor and motor neuron death. Downstream of Hsp90 inhibition, P2X7 receptor activated the phosphatase and tensin homolog (TPEN), which in turn suppressed the pro-survival phosphatidyl inositol 3 kinase (PI3K)/Akt pathway, leading to Fas-dependent motor neuron apoptosis. Conditions altering the interaction between P2X7 receptor and Hsp90, such as recruitment of Hsp90 to other subcellular compartments under stress conditions, or nitration following oxidative stress can induce motor neuron death. These findings may have broad implications in neurodegenerative disorders, including amyotrophic lateral sclerosis, in which activation of P2X7 receptor may be involved in both autonomous and non-autonomous motor neurons death. Impact statement Here we show that a motor neuron specific pool of Hsp90 that is highly sensitive to geldanamycin inhibition represses ligand-independent activation of P2X7 receptor and is critical to motor neuron survival. Activation of P2X7 receptor by Hsp90 inhibition triggers motor neuron apoptosis through the activation of PTEN, which in turn inhibits the PI3 kinase/Akt survival pathway. Thus, inhibition of Hsp90 for therapeutic applications may have the unexpected negative consequence of decreasing the activity of trophic pathways in motor neurons. The inhibition of Hsp90 as a therapeutic approach may require the identification of the Hsp90 complexes involved in pathogenic processes and the development of inhibitors selective for these complexes.

APA, Harvard, Vancouver, ISO, and other styles

33

Connolly, Owen, Laura Le Gall, Gavin McCluskey, Colette G. Donaghy, William J. Duddy, and Stephanie Duguez. "A Systematic Review of Genotype–Phenotype Correlation across Cohorts Having Causal Mutations of Different Genes in ALS." Journal of Personalized Medicine 10, no. 3 (June 29, 2020): 58. http://dx.doi.org/10.3390/jpm10030058.

Full text

Abstract:

Amyotrophic lateral sclerosis is a rare and fatal neurodegenerative disease characterised by progressive deterioration of upper and lower motor neurons that eventually culminates in severe muscle atrophy, respiratory failure and death. There is a concerning lack of understanding regarding the mechanisms that lead to the onset of ALS and as a result there are no reliable biomarkers that aid in the early detection of the disease nor is there an effective treatment. This review first considers the clinical phenotypes associated with ALS, and discusses the broad categorisation of ALS and ALS-mimic diseases into upper and lower motor neuron diseases, before focusing on the genetic aetiology of ALS and considering the potential relationship of mutations of different genes to variations in phenotype. For this purpose, a systematic review is conducted collating data from 107 original published clinical studies on monogenic forms of the disease, surveying the age and site of onset, disease duration and motor neuron involvement. The collected data highlight the complexity of the disease’s genotype–phenotype relationship, and thus the need for a nuanced approach to the development of clinical assays and therapeutics.

APA, Harvard, Vancouver, ISO, and other styles

34

Quessada, Cyril, Alexandra Bouscary, Frédérique René, Cristiana Valle, Alberto Ferri, Shyuan T. Ngo, and Jean-Philippe Loeffler. "Skeletal Muscle Metabolism: Origin or Prognostic Factor for Amyotrophic Lateral Sclerosis (ALS) Development?" Cells 10, no. 6 (June 9, 2021): 1449. http://dx.doi.org/10.3390/cells10061449.

Full text

Abstract:

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive and selective loss of motor neurons, amyotrophy and skeletal muscle paralysis usually leading to death due to respiratory failure. While generally considered an intrinsic motor neuron disease, data obtained in recent years, including our own, suggest that motor neuron protection is not sufficient to counter the disease. The dismantling of the neuromuscular junction is closely linked to chronic energy deficit found throughout the body. Metabolic (hypermetabolism and dyslipidemia) and mitochondrial alterations described in patients and murine models of ALS are associated with the development and progression of disease pathology and they appear long before motor neurons die. It is clear that these metabolic changes participate in the pathology of the disease. In this review, we summarize these changes seen throughout the course of the disease, and the subsequent impact of glucose–fatty acid oxidation imbalance on disease progression. We also highlight studies that show that correcting this loss of metabolic flexibility should now be considered a major goal for the treatment of ALS.

APA, Harvard, Vancouver, ISO, and other styles

35

Sonoo, Masahiro. "Motor Neuron Disease." Spinal Surgery 25, no. 3 (2011): 234–41. http://dx.doi.org/10.2531/spinalsurg.25.234.

Full text

APA, Harvard, Vancouver, ISO, and other styles

36

Jackson, Carlayne E., and Jeffrey Rosenfeld. "Motor Neuron Disease." Physical Medicine and Rehabilitation Clinics of North America 12, no. 2 (May 2001): 335–52. http://dx.doi.org/10.1016/s1047-9651(18)30073-1.

Full text

APA, Harvard, Vancouver, ISO, and other styles

37

Dimachkie, Mazen M., and Richard J. Barohn. "Motor Neuron Disease." Neurologic Clinics 33, no. 4 (November 2015): xiii—xiv. http://dx.doi.org/10.1016/j.ncl.2015.09.001.

Full text

APA, Harvard, Vancouver, ISO, and other styles

38

Mills, K. R. "Motor neuron disease." Brain 118, no. 4 (1995): 971–82. http://dx.doi.org/10.1093/brain/118.4.971.

Full text

APA, Harvard, Vancouver, ISO, and other styles

39

Mitchell, J. D. "Motor neuron disease." Neuromuscular Disorders 6, no. 2 (March 1996): 141. http://dx.doi.org/10.1016/s0960-8966(96)90024-3.

Full text

APA, Harvard, Vancouver, ISO, and other styles

40

Dimachkie, Mazen M., and Richard J. Barohn. "Motor Neuron Disease." Neurologic Clinics 33, no. 4 (November 2015): i. http://dx.doi.org/10.1016/s0733-8619(15)00090-0.

Full text

APA, Harvard, Vancouver, ISO, and other styles

41

Leigh, P. N., and K. Ray-Chaudhuri. "Motor neuron disease." Journal of Neurology, Neurosurgery & Psychiatry 57, no. 8 (August 1, 1994): 886–96. http://dx.doi.org/10.1136/jnnp.57.8.886.

Full text

APA, Harvard, Vancouver, ISO, and other styles

42

Westarp, M. E., and H. H. Kornhuber. "Motor neuron disease." Journal of Neurology, Neurosurgery & Psychiatry 58, no. 2 (February 1, 1995): 269. http://dx.doi.org/10.1136/jnnp.58.2.269.

Full text

APA, Harvard, Vancouver, ISO, and other styles

43

Griffin, John W. "Motor neuron disease." Trends in Neurosciences 18, no. 11 (November 1995): 513–14. http://dx.doi.org/10.1016/0166-2236(95)90053-5.

Full text

APA, Harvard, Vancouver, ISO, and other styles

44

Liveson, Jay. "Motor Neuron Disease." New England Journal of Medicine 334, no. 18 (May 2, 1996): 1203. http://dx.doi.org/10.1056/nejm199605023341818.

Full text

APA, Harvard, Vancouver, ISO, and other styles

45

Kernich, Catherine A. "Motor Neuron Disease." Neurologist 15, no. 1 (January 2009): 49–50. http://dx.doi.org/10.1097/nrl.0b013e31818fb5a2.

Full text

APA, Harvard, Vancouver, ISO, and other styles

46

Kristensen, O., and B. Melgaard. "MOTOR NEURON DISEASE." Acta Neurologica Scandinavica 56, no. 4 (January 29, 2009): 299–308. http://dx.doi.org/10.1111/j.1600-0404.1977.tb01437.x.

Full text

APA, Harvard, Vancouver, ISO, and other styles

47

Swash, M. "Motor neuron disease." Postgraduate Medical Journal 68, no. 801 (July 1, 1992): 533–37. http://dx.doi.org/10.1136/pgmj.68.801.533.

Full text

APA, Harvard, Vancouver, ISO, and other styles

48

Talbot, Kevin. "Motor neuron disease." Medicine 32, no. 11 (November 2004): 105–7. http://dx.doi.org/10.1383/medc.32.11.105.53361.

Full text

APA, Harvard, Vancouver, ISO, and other styles

49

Laing, Nigel G., Frank L. Mastaglia, and B. A. Kakulas. "Motor Neuron Disease." Trends in Neurosciences 17, no. 11 (January 1994): 505. http://dx.doi.org/10.1016/0166-2236(94)90145-7.

Full text

APA, Harvard, Vancouver, ISO, and other styles

50

BK, Binukumar, Susan Skuntz, Michaela Prochazkova, Sashi Kesavapany, Niranjana D. Amin, Varsha Shukla, Philip Grant, Ashok B. Kulkarni, and Harish C. Pant. "Overexpression of the Cdk5 inhibitory peptide in motor neurons rescue of amyotrophic lateral sclerosis phenotype in a mouse model." Human Molecular Genetics 28, no. 19 (May 9, 2019): 3175–87. http://dx.doi.org/10.1093/hmg/ddz118.

Full text

Abstract:

Abstract Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects motor nerve cells in the brain and the spinal cord. Etiological mechanisms underlying the disease remain poorly understood; recent studies suggest that deregulation of p25/Cyclin-dependent kinase 5 (Cdk5) activity leads to the hyperphosphorylation of Tau and neurofilament (NF) proteins in ALS transgenic mouse model (SOD1G37R). A Cdk5 involvement in motor neuron degeneration is supported by analysis of three SOD1G37R mouse lines exhibiting perikaryal inclusions of NF proteins and hyperphosphorylation of Tau. Here, we tested the hypothesis that inhibition of Cdk5/p25 hyperactivation in vivo is a neuroprotective factor during ALS pathogenesis by crossing the new transgenic mouse line that overexpresses Cdk5 inhibitory peptide (CIP) in motor neurons with the SOD1G37R, ALS mouse model (TriTg mouse line). The overexpression of CIP in the motor neurons significantly improves motor deficits, extends survival and delays pathology in brain and spinal cord of TriTg mice. In addition, overexpression of CIP in motor neurons significantly delays neuroinflammatory responses in TriTg mouse. Taken together, these data suggest that CIP may serve as a novel therapeutic agent for the treatment of neurodegenerative diseases.

APA, Harvard, Vancouver, ISO, and other styles

Journal articles on the topic 'Motoer Neuron Disease'

Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles