Academic literature on the topic 'Neurodegenerative'
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Journal articles on the topic "Neurodegenerative"
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Marín López, Alejandra Guadalupe, Justo Murguía Castillo, Rafael De Jesús Macías Vélez, and Martha Catalina Rivera Cervantes. "Neurodegeneración aguda y crónica un continuo en el establecimiento de los desórdenes neurodegenerativos." e-CUCBA 10, no. 19 (December 22, 2022): 175–82. http://dx.doi.org/10.32870/ecucba.vi19.277.
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As worldwide human population grows in number and gets older, disabilities derived from neurological disorders become morepresent. In addition to the lack of efforts directed to preventive actions against the occurrence and establishment of a neurologicaldisorder, will lead governmental institutions to face an increasing requirement for treatment and rehabilitations programs to dealwith consequences caused by these disorders. Demonstrating the importance that neuroscientists focus on the design of newparadigms that allow the identification of a potential prophylactic and therapeutic treatment for these disorders, is a key step. In thepresent work, authors did an overall bibliographical review and general description of the mechanisms involved on acute andchronic neurodegenerative damage, trying to show the common points on both kind of damage. Therefore, to identify andsubstantiate the key characteristics that link degenerative progression from an acute damage to the establishment of a chronicalneurological disorder. Highlighting the value of early interventions on acute neurological damage, centered on neuroprotection viacell signaling pathways that could mediate or prevent neuronal damage. Consequently, to spot and notice the repercussions andtranscendence that research in therapeutic strategies focus on mimic and potentiate the compensatory response unchained after aneurological damage, is a key factor to find new treatments for these disorders.
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Mandel, Silvia, and Moussa B. H. Youdim. "Catechin polyphenols: neurodegeneration and neuroprotection in neurodegenerative diseases." Free Radical Biology and Medicine 37, no. 3 (August 2004): 304–17. http://dx.doi.org/10.1016/j.freeradbiomed.2004.04.012.
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Petrozzi, Lucia, Giulia Ricci, Noemi J. Giglioli, Gabriele Siciliano, and Michelangelo Mancuso. "Mitochondria and Neurodegeneration." Bioscience Reports 27, no. 1-3 (June 13, 2007): 87–104. http://dx.doi.org/10.1007/s10540-007-9038-z.
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Many lines of evidence suggest that mitochondria have a central role in ageing-related neurodegenerative diseases. However, despite the evidence of morphological, biochemical and molecular abnormalities in mitochondria in various tissues of patients with neurodegenerative disorders, the question “is mitochondrial dysfunction a necessary step in neurodegeneration?” is still unanswered. In this review, we highlight some of the major neurodegenerative disorders (Alzheimer's disease, Parkinson's disease, Amyotrophic lateral sclerosis and Huntington's disease) and discuss the role of the mitochondria in the pathogenetic cascade leading to neurodegeneration.
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Bischof, Gérard N. "Tau-PET Bildgebung der Demenzerkrankungen." Angewandte Nuklearmedizin 45, no. 04 (December 2022): 266–72. http://dx.doi.org/10.1055/a-1712-6020.
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ZusammenfassungDie Ablagerung von Tau-Proteinen ist ein grundlegendes pathophysiologisches Merkmal vieler neurodegenerativer Demenzerkrankungen. Die Entwicklung sensitiver Tau-PET Tracer in den letzten Jahren hat die Lokalisation von Tau-Ablagerungen in unterschiedlichen klinischen neurodegenerativen Phänotypen in vivo ermöglicht. Bei der Alzheimer Demenz sind die räumlichen Muster der Tau-Pathologie in temporalen, parietalen und frontalen Regionen mit der Neurodegeneration und klinischen Symptomatik korreliert. Des Weiteren zeigen sich Zusammenhänge mit der Schwere der kognitiven Beeinträchtigung und der gemessenen Tau-Last, sodass Tau-PET in Zukunft einen hohen Nutzen in der klinischen Anwendung zugesprochen werden könnte. Bei primären Tauopathien, neurodegenerative Erkrankungen wie z.B. PSP und CBD, deren dominantes pathophysiologisches Merkmal die Ansammlung von Tau-Proteinen im Gehirn sind, steht die Validierung der wissenschaftlich genutzten Tau-PET Tracer noch aus, aber erste Hinweise aus Studien mit Tau-PET Tracern der zweiten Generation sind vielversprechend. Diese zeigen, dass die räumliche Verteilung der Tracer-Anreicherung bei primären Tauopathien von dem räumlichen Verteilungsmuster bei der Alzheimer Demenz unterschieden werden kann.Dennoch fehlen aktuell wichtige Validierungsstudien, die in größeren Kohorten den direkten klinischen Nutzen der Tau-PET Bildgebung belegen. Auf der anderen Seite haben die bisherigen wissenschaftlichen Erkenntnisse, die durch die Tau-PET Bildgebung gewonnen wurden, bereits einen wesentlichen Beitrag zum Zusammenhang von Tau-Pathologie und Neurodegeneration geleistet.
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Brkic, Marjana, Sriram Balusu, Claude Libert, and Roosmarijn E. Vandenbroucke. "Friends or Foes: Matrix Metalloproteinases and Their Multifaceted Roles in Neurodegenerative Diseases." Mediators of Inflammation 2015 (2015): 1–27. http://dx.doi.org/10.1155/2015/620581.
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Neurodegeneration is a chronic progressive loss of neuronal cells leading to deterioration of central nervous system (CNS) functionality. It has been shown that neuroinflammation precedes neurodegeneration in various neurodegenerative diseases. Matrix metalloproteinases (MMPs), a protein family of zinc-containing endopeptidases, are essential in (neuro)inflammation and might be involved in neurodegeneration. Although MMPs are indispensable for physiological development and functioning of the organism, they are often referred to as double-edged swords due to their ability to also inflict substantial damage in various pathological conditions. MMP activity is strictly controlled, and its dysregulation leads to a variety of pathologies. Investigation of their potential use as therapeutic targets requires a better understanding of their contributions to the development of neurodegenerative diseases. Here, we review MMPs and their roles in neurodegenerative diseases: Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), Huntington’s disease (HD), and multiple sclerosis (MS). We also discuss MMP inhibition as a possible therapeutic strategy to treat neurodegenerative diseases.
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Desai, Shyamal, Meredith Juncker, and Catherine Kim. "Regulation of mitophagy by the ubiquitin pathway in neurodegenerative diseases." Experimental Biology and Medicine 243, no. 6 (January 9, 2018): 554–62. http://dx.doi.org/10.1177/1535370217752351.
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Mitophagy is a cellular process by which dysfunctional mitochondria are degraded via autophagy. Increasing empirical evidence proposes that this mitochondrial quality-control mechanism is defective in neurons of patients with various neurodegenerative diseases such as Ataxia Telangiectasia, Alzheimer’s disease, Parkinson’s disease, and Amyotrophic Lateral Sclerosis. Accumulation of defective mitochondria and the production of reactive oxygen species due to defective mitophagy have been identified as causes underlying neurodegenerative disease pathogenesis. However, the reason mitophagy is defective in most neurodegenerative diseases is unclear. Like mitophagy, defects in the ubiquitin/26S proteasome pathway have been linked to neurodegeneration, resulting in the characteristic protein aggregates often seen in neurons of affected patients. Although initiation of mitophagy requires a functional ubiquitin pathway, whether defects in the ubiquitin pathway are causally responsible for defective mitophagy is not known. In this mini-review, we introduce mitophagy and ubiquitin pathways and provide a summary of our current understanding of the regulation of mitophagy by the ubiquitin pathway. We will then briefly review empirical evidence supporting mitophagy defects in neurodegenerative diseases. The review will conclude with a discussion of the constitutively elevated expression of ubiquitin-like protein Interferon-Stimulated Gene 15 (ISG15), an antagonist of the ubiquitin pathway, as a potential cause of defective mitophagy in neurodegenerative diseases. Impact statement Neurodegenerative diseases place an enormous burden on patients and caregivers globally. Over six million people in the United States alone suffer from neurodegenerative diseases, all of which are chronic, incurable, and with causes unknown. Identifying a common molecular mechanism underpinning neurodegenerative disease pathology is urgently needed to aid in the design of effective therapies to ease suffering, reduce economic cost, and improve the quality of life for these patients. Although the development of neurodegeneration may vary between neurodegenerative diseases, they have common cellular hallmarks, including defects in the ubiquitin-proteasome system and mitophagy. In this review, we will provide a summary of our current understanding of the regulation of mitophagy by the ubiquitin pathway and discuss the potential of targeting mitophagy and ubiquitin pathways for the treatment of neurodegeneration.
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Guerreiro, Serge, Anne-Laure Privat, Laurence Bressac, and Damien Toulorge. "CD38 in Neurodegeneration and Neuroinflammation." Cells 9, no. 2 (February 18, 2020): 471. http://dx.doi.org/10.3390/cells9020471.
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Neurodegenerative diseases are characterized by neuronal degeneration as well as neuroinflammation. While CD38 is strongly expressed in brain cells including neurons, astrocytes as well as microglial cells, the role played by CD38 in neurodegeneration and neuroinflammation remains elusive. Yet, CD38 expression increases as a consequence of aging which is otherwise the primary risk associated with neurodegenerative diseases, and several experimental data demonstrated that CD38 knockout mice are protected from neurodegenerative and neuroinflammatory insults. Moreover, nicotinamide adenine dinucleotide, whose levels are tightly controlled by CD38, is a recognized and potent neuroprotective agent, and NAD supplementation was found to be beneficial against neurodegenerative diseases. The aims of this review are to summarize the physiological role played by CD38 in the brain, present the arguments indicating the involvement of CD38 in neurodegeneration and neuroinflammation, and to discuss these observations in light of CD38 complex biology.
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Batista, Carla Ribeiro Alvares, Giovanni Freitas Gomes, Eduardo Candelario-Jalil, Bernd L. Fiebich, and Antonio Carlos Pinheiro de Oliveira. "Lipopolysaccharide-Induced Neuroinflammation as a Bridge to Understand Neurodegeneration." International Journal of Molecular Sciences 20, no. 9 (May 9, 2019): 2293. http://dx.doi.org/10.3390/ijms20092293.
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A large body of experimental evidence suggests that neuroinflammation is a key pathological event triggering and perpetuating the neurodegenerative process associated with many neurological diseases. Therefore, different stimuli, such as lipopolysaccharide (LPS), are used to model neuroinflammation associated with neurodegeneration. By acting at its receptors, LPS activates various intracellular molecules, which alter the expression of a plethora of inflammatory mediators. These factors, in turn, initiate or contribute to the development of neurodegenerative processes. Therefore, LPS is an important tool for the study of neuroinflammation associated with neurodegenerative diseases. However, the serotype, route of administration, and number of injections of this toxin induce varied pathological responses. Thus, here, we review the use of LPS in various models of neurodegeneration as well as discuss the neuroinflammatory mechanisms induced by this toxin that could underpin the pathological events linked to the neurodegenerative process.
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Werdann, Michelle, and Yong Zhang. "Circadian rhythm and neurodegenerative disorders." Brain Science Advances 6, no. 2 (June 2020): 71–80. http://dx.doi.org/10.26599/bsa.2020.9050006.
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The circadian clock controls daily rhythms in animal physiology, metabolism, and behavior, such as the sleep‐wake cycle. Disruption of circadian rhythms has been revealed in many diseases including neurodegenerative disorders. Interestingly, patients with many neurodegenerative diseases often show problems with circadian clocks even years before other symptoms develop. Here we review the recent studies identifying the association between circadian rhythms and several major neurodegenerative disorders. Early intervention of circadian rhythms may benefit the treatment of neurodegeneration.
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Juranek, Judyta, Rashmi Ray, Marta Banach, and Vivek Rai. "Receptor for advanced glycation end-products in neurodegenerative diseases." Reviews in the Neurosciences 26, no. 6 (December 1, 2015): 691–98. http://dx.doi.org/10.1515/revneuro-2015-0003.
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AbstractThis review, for the first time, aims to summarize the current knowledge in the emerging field of RAGE (receptor for advanced glycation end-products) studies in neurodegeneration and neurodegenerative diseases. RAGE, a member of the multiligand cell surface immunoglobulin family, has been implicated in numerous pathological conditions – from diabetes and cardiovascular diseases to tumors and neurodegenerative disorders, such as Alzheimer’s disease, familial amyloid polyneuropathy, diabetic neuropathy, Parkinson’s disease, and Huntington’s disease. Until now, the detailed mechanisms of the contribution of RAGE to neurodegeneration remain elusive; however, mounting evidence suggests that its detrimental actions are triggered by its ligand interactions and contribute to increased neuroinflammation, neuronal degeneration, and apoptosis. Deciphering the role of RAGE in neurodegenerative disorders will be a milestone in our basic understanding of the mechanisms involved in the pathogenesis of neurodegeneration, helping to delineate molecular links between complex RAGE signaling pathways and neuronal dysfunction and neurodegeneration.
Dissertations / Theses on the topic "Neurodegenerative"
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Querol, Vilaseca Marta. "Novel digital neuropathology methods applied to neurodegenerative diseases." Doctoral thesis, Universitat Autònoma de Barcelona, 2020. http://hdl.handle.net/10803/671999.
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Cada tres segons alguna persona al món desenvolupa demència. Les malalties neurodegeneratives, amb la malaltia d’Alzheimer (MA), la malaltia de Parkinson i la demència frontotemporal com les formes més predominants, són un grup de desordres que afecten a milions de persones arreu del món. La neuropatologia de mostres post-mortem humanes encara és necessària per esclarir els mecanismes subjacents alterats en les malalties neurodegeneratives. En aquesta tesis hem combinat immunoassaigs clàssics, tècniques de microscopia òptica i eines computacionals automatitzades per investigar la neuroinflamació i l’acumulació anormal de proteïnes en les malalties neurodegeneratives. En particular, hem investigat alteracions dels astròcits i cèl·lules glials en la MA i altres taupaties. Hem aprofitat les tècniques de super-resolució emergents i hem aplicat i optimitzat l’array tomography (AT) combinant-lo amb stimulated emission depletion microscopy (STED) per estudiar les plaques d’amiloide humanes a nivell nanomètric. Finalment, hem aplicat mètodes digitals i l’AT per analitzar quantitativament els canvis cerebrals en un pacient tractat amb un inhibidor de BACE-1. Aquests tres treballs il·lustren com les eines digitals poden integrar-se amb els mètodes neuropatològics clàssics per la investigació de la MA i altres malalties neurodegeneratives.Cada tres segundos alguien en el mundo desarrolla demencia. Las enfermedades neurodegenerativas, con la enfermedad de Alzheimer (EA), enfermedad de Parkinson y la demencia frontotemporal como las formas más prevalentes, son un grupo de desórdenes que afectan a millones de personas alrededor del mundo. La neuropatología de muestras post-mortem humanas aún es necesaria para esclarecer los mecanismos subyacentes alterados en las enfermedades neurodegenerativas. En esta tesis hemos combinado immunoensayos clásicos, técnicas de microscopía óptica y herramientas computacionales automatizadas para investigar la neuroinflamación y la acumulación anormal de proteínas en las enfermedades neurodegenerativas. En particular, hemos investigado alteraciones de los astrocitos y células gliales en la EA y otras taupatías. Hemos aprovechado las técnicas de super-resolución emergentes y hemos aplicado y optimizado el array tomography (AT) combinándolo con stimulated emission depletion microscopy (STED) para estudiar las placas de amiloide humanas a nivel nanométrico. Finalmente, hemos aplicado métodos digitales y AT para analizar cuantitativamente los cambios cerebrales en un paciente tratado con un inhibidor de BACE-1. Estos tres trabajos ilustran cómo las herramientas digitales pueden integrarse con los métodos neuropatológicos clásicos para la investigación de la EA y otras enfermedades neurodegenerativas.
Every 3 seconds someone in the world develops dementia. Neurodegenerative diseases (NDDs) with Alzheimer's disease (AD), Parkinson's disease (PD) and frontotemporal dementia (FTD) as the most prevalent forms are a group of disorders affecting millions of people worldwide. Neuropathology of post-mortem human samples is still needed to elucidate the underlying altered mechanisms of NDDs. In this thesis we combined classical immunoassays, light microscopy techniques and automated computational tools in order to investigate neuroinflammation and abnormal protein accumulation in NDDs. In particular, we investigated astrocytic and glial abnormalities in AD and other tauopathies. We took advantage of emerging super-resolution techniques and applied and optimized array tomography (AT) combined with stimulated emission depletion microscopy (STED) to study human amyloid plaques at a nanoscale level. Finally, we applied digital methods and AT to quantitative analyse the brain changes in a patient treated with a BACE-1 inhibitor. These three works illustrate how digital tools can be integrated with classical neuropathological methods in the investigation of AD and other NDDs.
Universitat Autònoma de Barcelona. Programa de Doctorat en Neurociències
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Ispierto, González Lourdes. "Aplicaciones de la ultrasonografía transcraneal en los trastornos del movimiento." Doctoral thesis, Universitat Autònoma de Barcelona, 2021. http://hdl.handle.net/10803/673205.
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El diagnòstic de la malaltia de Parkinson (MP) i de la major part de trastorns del moviment es basa fonamentalment en criteris clínics. No obstant això, existeix un important solapament fenotípic i anatomopatològic que pot dificultar en gran manera el diagnòstic diferencial, especialment en fases inicials de la malaltia.
La ultrasonografía transcranial ha sorgit com una tècnica no invasiva, de ràpida execució i baix cost econòmic, de gran utilitat com a eina complementària en el diagnòstic diferencial dels trastorns del moviment. La hipòtesi plantejada en aquesta tesi doctoral és que aquesta tècnica pot ser útil en la pràctica clínica diària d’una unitat de trastorns del moviment (UTM) per a l’estudi de la MP, el seu diagnòstic diferencial amb altres quadres que cursin amb tremolor i/o parkinsonisme i l’estudi d’altres trastorns del moviment hipercinètics com la síndrome de Gilles de la Tourette (SGT).
Per a demostrar aquesta hipòtesi s’han dut a terme 4 treballs amb diferents grups mostrals procedents d’una consulta d’UTM i controls sans. Es van analitzar variables sonogràfiques com l’àrea de substància nigra (SN) hiperecogènica, tamany del tercer ventricle i de la banya frontal del ventricle lateral, ecogenicitat dels nuclis del rafe i del nucli lenticular. En el primer treball es va estudiar un grup control sa per a establir els punts de tall patològics per a les variables sonogràfiques quantitatives i es va analitzar la utilitat de les troballes sonogràfiques per al diagnòstic diferencial de la MP enfront d’altres patologies que cursen amb tremolor i/o parkinsonisme. En el segon treball es va intentar identificar si alguna variable sonogràfica servia com a marcador d’un fenotip clínic concret en la MP (major severitat, predomini tremòric o rígid-acinètic, presència de símptomes no motors). En el tercer treball es va comprovar la utilitat de la tècnica, comparada amb tècniques de neuroimatge convencional, per a la comprovació postoperatòria precoç dels elèctrodes d’estimulació cerebral profunda (ECP) en el nucli subtalàmic (NST) en la MP. En el quart treball es van estudiar les troballes sonogràfiques en pacients amb SGT.
S’ha demostrat que l’estudi sonogràfic de l’àrea de SN hiperecogènica és útil per al diagnòstic diferencial entre MP, tremolor i altres parkinsonismes (atípics i secundaris), l’estudi del tamany ventricular i l’ecogenicitat del lenticular són útils per a identificar parkinsonismes atípics. Una SN hiperecogènica, una hiperecogenicitat lenticular i un major tamany del ventricle lateral correlacionen amb majors puntuacions en l’escala Hoehn i Yahr; aquest últim s’associa també a una major afectació axial i de la marxa. Pacients amb complicacions motores mostren majors àrees de SN, la grandària del tercer ventricle va ser major si hi havia al·lucinacions visuals i el ventricle lateral va ser major en pacients amb hiposmia, el rafe va ser més sovint hipoecogènic en presència de depressió. La sonografía transcranial és útil per a la comprovació postoperatòria precoç dels elèctrodes d’ECP en el NST. En el SGT s’ha detectat un augment significatiu de la hiperecogenicitat lenticular en comparació amb controls sans.
Per tant, els resultats d’aquesta recerca donen suport a l’ús de la ultrasonografía transcranial per a l’estudi dels trastorns del moviment en la pràctica clínica habitual d’una UTM. Són necessàries noves línies de recerca destinades a corroborar aquests resultats i ampliar l’estudi a altres trastorns del moviment poc explorats fins ara.El diagnóstico de la enfermedad de Parkinson (EP) y de la mayor parte de trastornos del movimiento se basa fundamentalmente en criterios clínicos. Sin embargo, existe un importante solapamiento fenotípico y anatomopatológico que puede dificultar en gran medida el diagnóstico diferencial, especialmente en fases iniciales de la enfermedad. La ultrasonografía transcraneal ha surgido como una técnica no invasiva, de rápida ejecución y bajo coste económico, de gran utilidad como herramienta complementaria en el diagnóstico diferencial de los trastornos del movimiento. La hipótesis planteada en esta tesis doctoral es que esta técnica puede ser útil en la práctica clínica diaria de una unidad de trastornos del movimiento (UTM) para el estudio de la EP, su diagnóstico diferencial con otros cuadros que cursen con temblor y/o parkinsonismo y el estudio de otros trastornos del movimiento hipercinéticos como el síndrome de Gilles de la Tourette (SGT). Para demostrar esta hipótesis se han llevado a cabo 4 trabajos con diferentes grupos muestrales procedentes de una consulta de UTM y controles sanos. Se analizaron variables sonográficas como el área de sustancia negra (SN) hiperecogénica, tamaño del tercer ventrículo y del asta frontal del ventrículo lateral, ecogenicidad de los núcleos del rafe y del núcleo lenticular. En el primer trabajo se estudió un grupo control sano para establecer los puntos de corte patológicos para las variables sonográficas cuantitativas y se analizó la utilidad de los hallazgos sonográficos para el diagnóstico diferencial de la EP frente a otras patologías que cursan con temblor y/o parkinsonismo. En el segundo trabajo se intentó identificar si alguna variable sonográfica servía como marcador de un fenotipo clínico concreto en la EP (mayor severidad, predominio tremórico o rígido-acinético, presencia de síntomas no motores). En el tercer trabajo se comprobó la utilidad de la técnica, comparada con técnicas de neuroimagen convencional, para la comprobación postoperatoria precoz de los electrodoimulación cerebral profunda (ECP) en el núcleo subtalámico en la EP. En el cuarto trabajo se estudiaron los hallazgos sonográficos en pacientes con SGT. Se ha demostrado que el estudio sonográfico del área de SN hiperecogénica es útil para el diagnóstico diferencial entre EP, temblor y otros parkinsonismos (atípicos y secundarios), el estudio del tamaño ventricular y la ecogenicidad del lenticular son útiles para identificar parkinsonismos atípicos. Una SN hiperecogénica, una hiperecogenicidad lenticular y un mayor tamaño del ventrículo lateral correlacionan con mayores puntuaciones en la escala Hoehn y Yahr; éste último se asocia también a una mayor afectación axial y de la marcha. Pacientes con complicaciones motoras muestran mayores áreas de SN, el tamaño del tercer ventrículo fue mayor si había alucinaciones visuales y el del ventrículo lateral fue mayor en pacientes con hiposmia, el rafe fue más frecuentemente hipoecogénico en presencia de depresión. La sonografía transcraneal es útil para la comprobación postoperatoria precoz de los electrodos de ECP en el NST. En el SGT se ha detectado un aumento significativo de la hiperecogenicidad lenticular en comparación con controles sanos. Por tanto, los resultados de esta investigación apoyan el uso de la ultrasonografía transcraneal para el estudio de los trastornos del movimiento en la práctica clínica habitual de una unidad de trastornos del movimiento. Son necesarias nuevas líneas de investigación destinadas a corroborar estos resultados y ampliar el estudio a otros trastornos del movimiento poco explorados hasta la fecha.
The diagnosis of Parkinson's disease (PD) and most movement disorders is based mainly on clinical criteria. However, there is a significant phenotypic and anatomopathological overlap that can make differential diagnosis very difficult, especially in the early stages of the disease. Transcranial ultrasonography has emerged as a non-invasive technique, of rapid execution and low economic cost, very useful as a complementary tool in the differential diagnosis of movement disorders. The hypothesis put forward in this doctoral thesis is that this technique may be useful in the daily clinical practice of a movement disorders unit (MDU) for the study of PD, its differential diagnosis with other conditions with tremor and/or parkinsonism and the study of other hyperkinetic movement disorders such as Gilles de la Tourette syndrome (GTS). In order to demonstrate this hypothesis, four studies have been carried out with different sample groups from a UTM outpatient consultation, and healthy controls. Sonographic variables such as the area of hyperechogenic substantia nigra (SN), size of the third ventricle and the frontal shaft of the lateral ventricle, ecogenicity of raphe nuclei and lenticular nuclei were analysed. In the first work a healthy control group was studied to establish the pathological cut-off points for the quantitative sonographic variables and the usefulness of the sonographic findings for the differential diagnosis of PD against other pathologies with tremor and/or parkinsonism was analysed. In the second work, an attempt was made to identify whether any sonographic variable served as a marker for a particular clinical phenotype in PD (greater severity, predominance of tremor or rigid-akinetic, presence of non-motor symptoms). In the third study, the usefulness of the technique, compared to conventional neuroimaging techniques, for early postoperative testing of deep brain stimulation (DBS) electrodes in the subthalamic nucleus (STN) in PD was tested. In the fourth study, sonographic findings were studied in patients with GTS. Sonographic study of the hyperechogenic SN area has been shown to be useful for the differential diagnosis between PD, tremor and other parkinsonisms (atypical and secondary), the study of ventricular size and lenticular ecogenicity are useful to identify atypical parkinsonisms. Hyperechogenic SN, lenticular hyperechogenicity and larger lateral ventricle size correlate with higher scores on the Hoehn and Yahr scale; the latter is also associated with greater axial and gait involvement. Patients with motor complications show greater areas of SN, the size of the third ventricle was larger if there were visual hallucinations and the lateral ventricle was larger in patients with hyposmia, the lenticular was more frequently hyperechogenic in the presence of depression. Transcranial sonography is useful for early postoperative testing of DBS electrodes in the STN. A significant increase in lenticular hyperechogenicity has been detected in the GTS compared to healthy controls. Therefore, the results of this research support the use of transcranial ultrasonography for the study of movement disorders in the routine clinical practice of a movement disorders unit. New lines of research are needed to corroborate these results and extend the study to other movement disorders that have been little explored to date.
Universitat Autònoma de Barcelona. Programa de Doctorat en Medicina
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O'Brien-Brown, James. "Novel P2X7 Receptor Ligands." Thesis, The University of Sydney, 2019. https://hdl.handle.net/2123/21280.
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The P2X7 receptor (P2X7R) is a purinergic receptor that plays a central role in the inflammatory response. Activation of the P2X7R releases pro-inflammatory cytokines such as interleukin 1β (IL-1β), which have been shown to underlie the pathogenesis of a number of neurodegenerative disorders. Consequently, the development of a CNS penetrant P2X7R antagonist is considered a promising target for the inhibition of neurodegenerative diseases. A series of P2X7R antagonists were synthesised to investigate which structural features of the hydrophobic moiety dictated binding site selectivity (orthosteric vs allosteric), and potency data are available for derivatives synthesised; assays to assess binding site selectivity have not currently been undertaken. To assist future pharmacological analyses, fluorescent probes based on lead compounds from the aryl cyanoguanidine and adamantyl benzamide P2X7R antagonist series were synthesised, and antagonist potency and binding affinity data for a number of derivatives are reported. Based on the original structure-activity relationship (SAR) study of the adamantyl cyanoguanidine series, a range of heterobicyclic adamantyl cyanoguanidine analogues were synthesised in order to refine the pharmacophore for potent P2X7R antagonism. The adamantyl indazoles 302 and 303 (IC50 = 18.6 ± 0.5 nM and 22.2 ± 6 nM respectively) were equipotent to the lead 19, and SAR data from this series has identified several structural requirements for potent P2X7R antagonism. Attempts to develop radioligands for visualising P2X7R expression in vivo are reported. The trifluorinated adamantyl benzamide [11C]SMW139 was progressed into first-in-human studies as a radiodiagnostic probe for identifying active areas of neuroinflammation in patients with relapsing-remitting multiple sclerosis (RRMS), with data from the small cohort suggesting it did so successfully. Further studies in larger cohorts are currently in progress.
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Sanabra, Palau Cristina. "AMPc i neuroinflamació: Identificació de proteïnes implicades en la regulació dels nivells d’AMPc en l’encefalomielitis autoimmune experimental." Doctoral thesis, Universitat de Barcelona, 2011. http://hdl.handle.net/10803/79038.
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L'AMPc té un paper clau com a missatger intracel.lular regulant la transmissió dels senyals extracel•lulars en diferents teixits i controlant múltiples processos cel lulars. Els nivells intracel.lulars d'AMPc es controlen mitjançant la seva síntesi, catalitzada per l'enzim adenilat ciclasa, i mitjançant la seva degradació a través de l'acció de les fosfodiesterases (PDE) de nucleòtids cíclics. Hi ha 11 famílies de PDEs. La PDE4 representa a una família de fosfodiesterases específiques d'AMPc formada per quatre gens paràlegs (PDE4-D), cadascun dels quals és capaç de generar múltiples variants d’splicing. La PDE4A, la PDE4B i la PDE4D es troben expressades en diferents tipus de cèl lules inflamatòries on tenen un important paper com reguladores dels processos inflamatoris. La inhibició selectiva, tant in vitro com in vivo, de PDEs ha demostrat tenir diferents efectes antiinflamatoris.
En aquest treball es mostra la implicació de la isoforma PDE4B, i en concret la seva variant de splicing PDE4B2, durant el procés neuroinflamatori del model animal d’Esclerosis Múltiple, l’Encefalomielitis Autoimmune Experimental (d’EAE). Els resultats mostren un augment de l’expressió de l’ARNm de PDE4B2 a la medul•la espinal de ratolins EAE que correlaciona amb l’expressió d’alguns marcadors inflamatoris de forma dependent a la simptomatologia clínica dels animals. També s’observa que l’enzim PDE4B es trova localitzat principalment en cèl•lules presentadores d’antigen (APCs) com les cèl•lules dendrítques i els macròfags/micròglia. A més, els ratolins PDE4B-/- mostren una aparició temprana dels símptomes clínics en comparació amb els ratolins wildtype, amb alteracions en l’expressió de l’ARNm d’algunes citocines. L’alteració selectiva de la PDE4B2 en el model d’EAE en ratolí i la seva participació en el desenvolupament de la malaltia com s’ha observat en els animals PDE4B-/- presenta noves possibilitats sobre l’ús d’inhibidors selectius per les diverses isoformes (i variants d’splicing) tant per aplicacions terapèutiques com per investigar mecanismes d’inflamació en malalties neurodegeneratives.Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis that courses with neuroinflammation, axonal damage and demyelination. The model is characterized by T- and B-cell responses to myelin oligodendrocyte glycoprotein which produce a wide range of pro- and anti-inflammatory cytokines. The modulation of cAMP levels through pharmacological manipulation of phosphodiesterases (PDEs) provokes profound anti-inflammatory responses. In the EAE model, amelioration of the clinical signs and delayed onset is observed after PDE4 inhibition and the PDE4B gene has been related to the inflammatory immune response in mice. Here we analyzed post-immunization changes in the expression of mRNA coding for the PDE4B2 splice variant by semiquantitative real-time PCR and in situ hybridization. The results showed an upregulation of PDE4B2 mRNA in the spinal cord of EAE mice which correlates with FoxP3 and TGF-β mRNAs expression in a score-dependent manner. We also found that PDE4B enzyme is mainly localized in antigen-presenting cells (APCs) such as dendritic cells and microglia/macrophages. PDE4B-/- mice show an earlier onset of the disease compared to wildtype mice, with alterations in some cytokine mRNA expression. The results point to a protective role of the PDE4B enzyme and PDE4B2 splice variant in particular, during EAE pathogenesis by modulating cAMP levels in APCs and controlling the cytokine environment for T-cell differentiation.
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Tell, Martí Gemma. "Rol del gen de pigmentació MC1R en la susceptibilitat a malalties neurodegeneratives." Doctoral thesis, Universitat de Barcelona, 2018. http://hdl.handle.net/10803/586171.
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El gen MC1R (codi OMIM: #155555) codifica pel receptor de la melanocortina 1 (MC1R) que s’expressa majoritàriament a la membrana dels melanòcits i està implicat en la regulació de la síntesi de melanina. El gen MC1R és clau en la regulació del color de la pell i el cabell i és el responsable de controlar la quantitat relativa de síntesi d’eumelanina i feomelanina. Aquest gen és altament polimòrfic, s’hi han identificat més de 100 variants no sinònimes, però l’alteració funcional que provoquen en la proteïna la majoria d’elles és desconeguda. No obstant, hi ha 9 d’aquestes variants: p.V60L, p.D84E, p.V92M, p.R142H, p.R151C, p.I155T, p.R160W, p.R163Q i p.D294H que presenten una freqüència al·lèlica (MAF) > 0,01 en diferents poblacions caucàsiques d’ètnia blanca i que han estat àmpliament estudiades tant a nivell epidemiològic com a nivell funcional. Entre aquestes, hi ha 6 variants al·lèliques que s’han definit com a variants de pèrdua de funció (LOF) (p.D84E, p.R142H, p.R151C, p.I155T, p.R160W i p.D294H), ja que disminueixen notablement la capacitat de senyalització del MC1R a través de la via de l’AMPc i impedeixen la síntesi d’eumelanina. Els individus portadors d’aquestes variants LOF presenten una forta associació amb el fenotip “color de cabell vermell” (cabell pèl-roig, un elevat nombre de pigues, una baixa capacitat per a bronzejar-se i una elevada sensibilitat a la RUV) i un augment del risc a desenvolupar càncer cutani.
L’anàlisi del transcriptoma de les cèl·lules cutànies portadores de variants LOF en MC1R va mostrar una desregulació constitutiva de gens implicats en les vies de senyalització de malalties neurodegeneratives i un augment de l’estrès oxidatiu. Donat que l’expressió del MC1R s’ha identificat també en les cèl·lules del sistema nerviós central i que un elevat nivell de dany oxidatiu s’ha observat en les àrees del cervell on hi ha neurodegeneració, varem hipotetitzar que el gen MC1R podria estar implicat en la patogènesi de les malalties neurodegeneratives.
Es van dissenyar dos estudis cas-control que incloïen 870 pacients de Parkinson, 525 pacients amb Alzheimer i 736 controls d’origen espanyol. A més, es va avaluar el gen MC1R com a factor modificador de l’edat d’aparició de la malaltia de Huntington, seqüenciant el gen en 600 pacients. Tant els anàlisis d’associació genotípica cas –control com els estudis de regressió múltiple es van dur a terme amb totes aquelles variants genètiques no sinònimes que presentaven una freqüència al·lèlica > 0,01 en els casos avaluats. Complementàriament, amb l’objectiu de posar en context biològic la signatura gènica associada a la pèrdua de funció del MC1R, es va realitzar un anàlisi de xarxes d’interacció proteïna-proteïna (PPI).
Els individus portadors de la variant LOF p.R160W presenten un augment del risc a desenvolupar Parkinson (OR=2,10; 95% IC: 1,18-3,73; p-valor ajustat = 0,009) i l’al·lel p.V92M de MC1R s’associa amb un augment del risc a desenvolupar la malaltia d’Alzheimer, especialment en aquells individus on el risc no pot atribuir-se a l’al·lel 4 de l’APOE. A més, el gen MC1R s’ha identificat com un factor modificador de l’edat d’inici de la malaltia de Huntington, ja que els casos portadors de l’al·lel p.R151C presenten una disminució de 5,13 anys respecte a l’edat mitjana d’aparició del Huntington. Concretament, el percentatge de variació en l’edat de debut atribuït a l’al·lel p.R151C és del 1,42%.
Els resultats de la present tesi indiquen que el gen MC1R està implicat en la patogènesi de les malalties neurodegeneratives, i que la pèrdua de funció del MC1R pot contribuir a la patogènesi d’aquestes a través d’un augment del dany oxidatiu, una disminució de la resposta antiinflamatòria i una desregulació de l’autofàgia.The melanocortin 1 receptor (MC1R) gene is a key regulator of skin and hair colour. Certain MC1R polymorphisms, which cause a loss of protein function, have been associated with red hair color (RHC) phenotype (red hair, fair skin, high UV sensitivity and low tanning capacity) and a higher risk of developing skin cancer. Although the MC1R is mainly expressed in melanocytes, it is also detected in several types of brain cells. We have identified that skin cells harbouring loss-of-function MC1R polymorphisms show a deregulation of genes involved in pathways related to neurodegenerative diseases, such as Parkinson’s disease (PD), Alzheimer’s disease (AD) and Huntington’s disease (HD). It has also been shown that skin cells with loss-of-function MC1R polymorphisms show a significantly greater oxidative damage, which is a physiological condition found in areas with neuronal degeneration. Based on these evidences, we hypothesize that MC1R gene could be involved in neurodegenerative diseases pathogenesis. We performed two case-control studies to elucidate the role of MC1R in PD and AD. We sequenced the MC1R gene in 870 PD patients, 525 AD patients and 736 controls from Spain. We assessed the role of MC1R as a modifier factor of age of onset (AOO) in HD, sequencing MC1R in 600 HD patients. We analyzed all non-synonymous MC1R variants with a minor allele frequency of at least 0.01. Additionally, we analyzed the gene signature identified in cells harbouring loss-of-function MC1R polymorphisms by protein-protein interaction network analysis (PPI) to identify biological processes related with loss of MC1R function. We found that the allele p.R160W of MC1R increases risk of PD (OR=2.10, 95% CI: 1.18-3.73, adjusted P = 0.009) and that the p.V92M MC1R allele is associated with AD (OR=1.99, 95% CI: 1.08-3.64, adjusted P = 0 026). Furthermore, the p.R151C MC1R allele modifies AOO in HD (Bonferroni-corrected P = 0.032), its effect explains 1.42% of the variance in AOO that cannot be accounted for by the expanded HD allele. Our results suggest that loss of MC1R function may be involved in neurodegenerative diseases etiology through an increased of oxidative damage, autophagy deregulation and reduced anti-inflammatory response.
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Garzón, Gómez Fernando. "Mecanismos neuroprotectores de la eritropoyetina (NeuroEPO) en enfermedades neurodegenerativas." Doctoral thesis, Universitat de Barcelona, 2019. http://hdl.handle.net/10803/667151.
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La eritropoyetina (EPO) es una glucoproteína inicialmente identificada como una hormona sintetizada y secretada por el riñón que regula la eritropoyesis. Muchos estudios experimentales muestran que la EPO tiene una acción neuroprotectora en el cerebro. En trastornos neurológicos agudos y crónicos, particularmente en apoplejía, lesión cerebral traumática, enfermedad de Alzheimer, enfermedad de Parkinson, esclerosis lateral amiotrófica y en accidente cerebro vascular, tiene efectos neuroprotectores. El objetivo de este estudio, utilizando un modelo in vitro, fue determinar cómo NeuroEPO, una variante de EPO con un bajo contenido de ácido siálico, protege a las neuronas de la acción excitotóxica del glutamato. Se utilizó cultivos neuronales primarios que se obtuvieron de la corteza cerebral de embriones de rata Wistar después de 17 días de gestación. La excitotoxicidad se indujo después de nueve días de cultivo in vitro mediante tratamiento con un medio que contenía glutamato 100 μM durante 15 minutos, para luego ser tratado con 100 ng / ml de NeuroEPO. Después de 24 h, el tratamiento mostró una disminución significativa (p <0,01) en la mortalidad, en comparación con las células tratadas con glutamato solo. El tratamiento NeuroEPO disminuyó la mortalidad y las células tendieron a reproducir las características morfológicas del control. Las imágenes obtenidas mediante microscopía de contraste de fases muestran que las neuronas tratadas con glutamato muestran una contracción corporal, pérdida de dendritas que no hacen contacto con las células vecinas y que NeuroEPO es capaz de preservar las características morfológicas del control. El estrés oxidativo inducido por el glutamato se reduce después del tratamiento con NeuroEPO. Las pruebas por inmunocitoquímica muestran que el cultivo es esencialmente puro en las neuronas, que el glutamato causa mortalidad celular, y que esto se evita parcialmente cuando en el medio de cultivo se añade NeuroEPO. Se analizó también la activación de las vías apoptóticas intrínsecas. La disminución en la relación Bcl-2 / Bax, fue determinante en la liberación de citocromo c desde la mitocondria hacia el citosol y en la expresión y la actividad de caspasa-3 observada en las células tratadas solo con glutamato. Estas alteraciones fueron evitadas en las células bajo tratamiento con NeuroEPO posterior al glutamato. Estos resultados permiten aseverar que NeuroEPO ejerce su función neuroprotectora actuando directamente sobre las neuronas una vez que se ha inducido la excitotoxicidad del glutamato, puede atenuar sustancialmente los cambios morfológicos causados por la excitotoxicidad inducida por glutamato en las neuronas, reduciendo el efecto neurotóxico que éste ejerce sobre la viabilidad neuronal, protege a las neuronas del estrés oxidativo y de la apoptosis inducidos por el glutamato mediante el manteniendo el equilibrio entre proteínas anti-apoptóticas (Bcl-2) y pro-apoptóticas (Bax), evitando la liberación al citosol del citocromo c y reduciendo la actividad de la caspasa-3. Los bajos niveles de ácido siálico de la NeuroEPO comparados con la rhEPO al parecer no afectan a la actividad neuroprotectora de la NeuroEPO.Erythropoietin (EPO) is a glycoprotein initially identified as a hormone synthesized and secreted by the kidney that regulates erythropoiesis. Many experimental studies show that EPO has a neuroprotective action in the brain. In acute and chronic neurological disorders, particularly in stroke, traumatic brain injury, Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis, it has neuroprotective effects. The objective of this study, using an in vitro model, was to determine how NeuroEPO, a variant of EPO with a low content of sialic acid, protects neurons from the toxic action of glutamate. Primary neuronal cultures that were obtained from the cerebral cortex of Wistar rat embryos after 17 days of gestation were used. The excitotoxicity was induced after nine days of in vitro culture by treatment with a medium containing 100 μM glutamate for 15 minutes. After 24 h, treatment with 100 ng of NeuroEPO / ml showed a significant decrease (p <0.01) in mortality, compared to cells treated with glutamate alone. The NeuroEPO treatment decreased mortality and tended to reproduce the morphological characteristics of the control. The oxidative stress induced by glutamate is reduced after treatment with NeuroEPO. The images obtained by phase contrast microscopy show that neurons treated with glutamate show a body contraction, loss of dendrites that do not make contact with neighboring cells, and NeuroEPO is capable of preserving the morphological characteristics of the control. Immunocytochemistry tests show that the culture is essentially pure in neurons, that glutamate causes cell mortality, and that this is partially avoided when NeuroEPO is added to the culture medium. The activation of the intrinsic apoptotic pathways was also analyzed. The decrease in the Bcl-2 / Bax ratio was decisive in the release of cytochrome from the mitochondria to the cytosol and in the expression and activity of caspase-3 observed in the cells treated with glutamate. These alterations were avoided in the cells under treatment with NeuroEPO. These results confirm that NeuroEPO has a protective effect against the neuronal damage induced by excitotoxicity, improving the antioxidant activity in the neuron and protecting it from oxidative stress; In addition, they show that NeuroEPO protects cortical neurons from glutamate-induced apoptosis by up-regulating Bcl-2 and inhibits the activation of caspase-3 induced by excitotoxicity due to glutamate.
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Vico, Rivero Tania. "El rol de los macrófagos en el Sindrome de Aicardi-Goutières." Doctoral thesis, Universitat de Barcelona, 2018. http://hdl.handle.net/10803/665198.
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El síndrome de Aicardi-Goutières (AGS) es una interferonopatía de tipo I que afecta mayoritariamente al cerebro y a la piel. Las personas afectadas tienen un nivel elevado de IFN-α en el líquido cefalorraquídeo y en el suero, tal y como sucede en una infección vírica congénita, pese a no detectar virus en ninguno de los casos estudiados. Aún no se conocen los detonantes de la aparición de la enfermedad, aunque todo apunta a que podría deberse a un factor exógeno y/o al propio background genético del individuo. En los últimos años se han identificado mutaciones en distintos genes que causan el AGS: TREX1, RNASA H2 (Subunidades A, B y C), SAMHD1, ADAR e IFIH1. Éstas suelen provocar la pérdida de la función de las proteínas, las cuales tienen en común su participación en la señalización y en el procesamiento de los ácidos nucleicos. En nuestro grupo se ha demostrado que el déficit funcional de proteínas que intervienen en la reparación del ADN, como Nbs1 y Trex1, alteran las funciones de los macrófagos, y consecuentemente los procesos donde éstos intervienen. Estas células son capaces de modular la respuesta inflamatoria gracias a sus actividades pro y antiinflamatorias. Por ello, la actividad de los macrófagos debe estar finamente regulada ya que el exceso en la respuesta pro- o antinflamatoria provoca daño en los tejidos y la aparición de enfermedades crónicas. Los macrófagos tienen un papel clave en el mantenimiento de la homeostasis, por lo que las alteraciones producidas en estas células podrían ser la base de la autoinmunidad en el AGS. En esta tesis se muestra el estudio de Samhd1 y del complejo RNasa H2 en los macrófagos y en las enfermedades autoinmunes. Estas proteínas participan en el metabolismo de los ácidos nucleicos y están relacionadas con el AGS. En mamíferos Samhd1 es la fosfohidrolasa encargada de regular negativamente la concentración de dNTPs intracelulares, mientras que el complejo RNasa H2 es la mayor fuente de actividad ribonucleasa H. De hecho, sus actividades son esenciales para el mantenimiento de la integridad genómica. En esta tesis se mostró que Samhd1 y el complejo RNasa H2 forman parte de los mecanismos de reparación del ADN que aseguran la supervivencia de los macrófagos durante la inflamación. Se determinó que los estímulos proinflamatorios inducían la expresión de Samhd1 en los macrófagos mientras que la expresión del complejo RNasa H2 era constitutiva. En ratones deficientes en Samhd1 y en el complejo RNasa H2 se observó un aumento en la expresión de genes estimulados por interferón (ISGs) en el corazón y en el cerebro, tal y como sucede en pacientes con AGS. Además, también se vio incrementada la expresión de estos genes en los macrófagos activados con estímulos proinflamatorios. Por otro lado, no pudimos detectar ningún efecto de las proteínas Samhd1 y RNasa H2 en la diferenciación, proliferación y en la activación de estas células. Sin embargo, cuando fueron activados de forma proinflamatoria, los macrófagos deficientes en estas proteínas presentaron más daño en el ADN respecto a los controles. Además, dicho daño fue causado por las grandes cantidades de especies reactivas de oxígeno (ROS) producidas por los propios macrófagos. Por otro lado, la falta de Samhd1 aumentó la severidad de la respuesta autoinmune la inducción del modelo in vivo de encefalomielitis autoinmune experimental (EAE). En conjunto estas observaciones sugieren que tanto Samhd1 como el complejo RNasa H2 forman parte de los mecanismos de protección de los macrófagos, que previenen el daño en el ADN causado por las grandes cantidades de ROS que estas células producen durante la respuesta inflamatoria.Aicardi-Goutières Syndrome (AGS) is a type I interferonopathy which affects brain and heart. Patients with AGS show high levels of IFN-α in cerebrospinal fluid and serum, which mimic a congenital virus infection. The trigger of this disease still is unknown but environmental factors and the genetic background could be potentially candidates. Currently, seven mutations have been described in patients with AGS: TREX1, RNASA H2 (Subunit A, B and C), SAMHD1, ADAR and IFIH1. Generally it causes the loss of function of the proteins, which are implicated in the signaling and metabolism of nucleic acids. Macrophages are an essential component of both innate and adaptive immunity. During immune response these cells play a dual role. Firstly macrophages produce pro-inflammatory mediators, including cytokines and reactive oxygen species (ROS), and engulf by phagocytosis pathogens and cell components. Secondly, when this damaging response is unnecessary macrophages acquire anti-inflammatory functions in order to induce tissue repair and the resolution of inflammation. The tightly regulation of pro- and anti-inflammatory activities in macrophages is essential to prevent tissue damage and chronic diseases. In our group we had demonstrated that proteins with DNA repair activities, as Nbs1 and Trex1, were required for macrophage functional activity. Macrophages are essential to maintain homeostasis and its alterations could be the origin of autoimmunity in AGS. In this thesis we showed that Samhd1 and RNase H2 protect macrophages during inflammation against DNA damage, caused by reactive oxygen species that they produce. Also we demonstrated that Samhd1 restrained the autoimmunity response in mice. These results reveal that Samhd1 and RNase h2 confer protection against DNA damage during inflammation in macrophages.
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Mosimann, Urs Peter. "Vision in neurodegenerative dementias." Thesis, University of Newcastle Upon Tyne, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.432515.
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Chen, Yongmei. "Excitotoxicity in neurodegenerative disorders." free to MU campus, to others for purchase, 1998. http://wwwlib.umi.com/cr/mo/fullcit?p9901225.
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Lobón, García Irene. "Detection of somatic variants from genomic data and their role in neurodegenerative diseases." Doctoral thesis, Universitat de Barcelona, 2019. http://hdl.handle.net/10803/667569.
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Somatic mutations are those that arise after the zygote is formed and are therefore inherited by a fraction of the cells of an individual. Their relevance in certain skin diseases has been known for almost half a decade and cancer, the most common disease caused by somatic mutations, has been extensively studied. Yet, their prevalence in healthy individuals as well as their putative role in other human disorders such as neurodegenerative diseases are still unanswered questions. Furthermore, accurate detection of somatic variants from bulk sequencing data still poses a technical challenge. This work focuses on detecting and circumventing the biases that hinder their identification. Using this knowledge, we identified somatic point mutations in the exomes of five different tissues from sporadic Parkinson disease patients. We also assessed the detection of somatic copy number variants from array CGH data using two tissues from Alzheimer disease patients. Finally, we participated in the identification of somatic variants in an extensive genomic dataset from a neurotypical individual.Las mutaciones somáticas son aquellas que surgen tras la formación del cigoto y son, por tanto, heredadas por una fracción de las células de un individuo. Su importancia en algunas enfermedades cutáneas se conoce desde hace casi medio siglo. El cáncer, la enfermedad más común causada por mutaciones somáticas, se ha estudiado extensamente. Sin embargo, su prevalencia en individuos sanos, así como su potencial relevancia en otras afecciones humanas, como las enfermedades neurodegenerativas, son cuestiones todavía por resolver. Asimismo, detectar variantes somáticas con precisión en datos de secuenciación de muestras homogeneizadas sigue siendo complejo técnicamente. Este trabajo se centra en la detección y resolución de los sesgos que dificultan su identificación. Aplicando este conocimiento, identificamos mutaciones somáticas de una sola base en datos de secuenciación del exoma de cinco tejidos diferentes de pacientes de la enfermedad de Parkinson. También evaluamos la detección de variantes de número de copia somáticas en datos de array CGH de dos tejidos de pacientes de Alzheimer. Finalmente, participamos en la identificación de variantes somáticas en un amplio conjunto de datos genómicos de un individuo neurotípico.
Books on the topic "Neurodegenerative"
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Neurodegenerative diseases. Austin, Tex: Landes Bioscience, 2011.
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Dominguez, Celia, ed. Neurodegenerative Diseases. Berlin, Heidelberg: Springer Berlin Heidelberg, 2010. http://dx.doi.org/10.1007/978-3-642-16758-4.
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Galimberti, Daniela, and Elio Scarpini, eds. Neurodegenerative Diseases. London: Springer London, 2014. http://dx.doi.org/10.1007/978-1-4471-6380-0.
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Hardiman, Orla, Colin P. Doherty, Marwa Elamin, and Peter Bede, eds. Neurodegenerative Disorders. Cham: Springer International Publishing, 2016. http://dx.doi.org/10.1007/978-3-319-23309-3.
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Hardiman, Orla, and Colin P. Doherty, eds. Neurodegenerative Disorders. London: Springer London, 2011. http://dx.doi.org/10.1007/978-1-84996-011-3.
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Galimberti, Daniela, and Elio Scarpini, eds. Neurodegenerative Diseases. Cham: Springer International Publishing, 2018. http://dx.doi.org/10.1007/978-3-319-72938-1.
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Ahmad, Shamim I., ed. Neurodegenerative Diseases. New York, NY: Springer US, 2012. http://dx.doi.org/10.1007/978-1-4614-0653-2.
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Beart, Philip, Michael Robinson, Marcus Rattray, and Nicholas J. Maragakis, eds. Neurodegenerative Diseases. Cham: Springer International Publishing, 2017. http://dx.doi.org/10.1007/978-3-319-57193-5.
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Fiskum, Gary, ed. Neurodegenerative Diseases. Boston, MA: Springer US, 1996. http://dx.doi.org/10.1007/978-1-4899-0209-2.
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Ahmad, Shamim I. Neurodegenerative Diseases. New York, NY: Springer US, 2012.
Find full textBook chapters on the topic "Neurodegenerative"
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Wendt, Julie, Colleen Considine, and Mikhail Kogan. "Neurodegenerative." In Integrative Geriatric Nutrition, 193–207. Cham: Springer International Publishing, 2021. http://dx.doi.org/10.1007/978-3-030-81758-9_9.
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Hilton, David A., and Aditya G. Shivane. "Neurodegenerative Disorders." In Neuropathology Simplified, 183–205. Cham: Springer International Publishing, 2015. http://dx.doi.org/10.1007/978-3-319-14605-8_12.
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Kim, Sang Eun, Jong Jin Lee, and Yoo Sung Song. "Neurodegenerative Diseases." In Clinical PET and PET/CT, 151–73. New York, NY: Springer New York, 2012. http://dx.doi.org/10.1007/978-1-4419-0802-5_13.
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D’incerti, Ludovico, Laura Farina, and Paolo Tortori-Donati. "Neurodegenerative Disorders." In Pediatric Neuroradiology, 723–40. Berlin, Heidelberg: Springer Berlin Heidelberg, 2005. http://dx.doi.org/10.1007/3-540-26398-5_14.
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J. MacKay, Robert. "Neurodegenerative Disorders." In Equine Neurology, 328–42. Hoboken, NJ: John Wiley & Sons, Inc, 2015. http://dx.doi.org/10.1002/9781118993712.ch26.
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Ozaki, Isamu, and Isao Hashimoto. "Neurodegenerative Disorders." In Clinical Applications of Magnetoencephalography, 209–43. Tokyo: Springer Japan, 2016. http://dx.doi.org/10.1007/978-4-431-55729-6_12.
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Biesalski, A. S., J. Becktepe, T. Bartsch, and C. Franke. "Neurodegenerative Erkrankungen." In Neurologische Pathophysiologie, 117–64. Berlin, Heidelberg: Springer Berlin Heidelberg, 2019. http://dx.doi.org/10.1007/978-3-662-56784-5_4.
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Potter, Nicholas T. "Neurodegenerative Disorders." In Molecular Pathology in Clinical Practice: Genetics, 177–87. Boston, MA: Springer US, 2009. http://dx.doi.org/10.1007/978-0-387-87374-9_15.
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Meyer, Michael Andrew. "Neurodegenerative Diseases." In Neurologic Disease, 161–75. Cham: Springer International Publishing, 2016. http://dx.doi.org/10.1007/978-3-319-39581-4_8.
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Clausen, Torben, José Luis Trejo, Mark P. Mattson, Alexis M. Stranahan, Joanna Erion, Rosa Maria Bruno, Stefano Taddei, and Melinda M. Manore. "Neurodegenerative Disease." In Encyclopedia of Exercise Medicine in Health and Disease, 637–40. Berlin, Heidelberg: Springer Berlin Heidelberg, 2012. http://dx.doi.org/10.1007/978-3-540-29807-6_145.
Full textConference papers on the topic "Neurodegenerative"
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Rezende, Maria Clara Lopes, Maria Luiza Franco de Oliveira, Júlia Campos Fabri, Maria Júlia Filgueiras Granato, Mariana Vanon Moreira, and Leandro Vespoli Campos. "Neuroprotective Effects of Creatine Supplementation in Neurodegenerative Diseases." In XIII Congresso Paulista de Neurologia. Zeppelini Editorial e Comunicação, 2021. http://dx.doi.org/10.5327/1516-3180.234.
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Introduction: Creatine is important in providing energy for the resynthesis of adenosine triphosphate (ATP) and in the deposition of intracellular energy, being present mainly in muscle fibers and in the brain. Supplementation with exogenous creatine can be used in neurodegenerative disorders that are related to bioenergetic deficits in the etiology and progression of the disease. Objective: Highlight the neuroprotective mechanisms of creatine supplementation in neurodegenerative diseases. Methods: In April 2021, a search was carried out on MEDLINE, with the descriptors: “Creatine” and “Neuroprotection”; and its variations, obtained in MeSH. Studies published in the last five years were included. Results: Of the 122 articles found, four were used in this work. They concluded that creatine supplementation contributes to brain bioenergetics by increasing phosphocreatine deposits, restoring mitochondrial functions and decreasing susceptibility to apoptosis. In addition, creatine intake shortly after the diagnosis of Huntington’s and Parkinson’s Diseases can be used as a complementary therapy, because improve performance in tasks of memory and intelligence. Finally, it buffers cellular concentrations of ATP, being a possible therapeutic strategy to delay or stop neurodegeneration diseases. Conclusion: Creatine promote important neuroprotective effect, but further studies on the subject are needed.
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Schott, Jonathan M. "MRI biomarkers in neurodegenerative disorders." In 2012 IEEE 9th International Symposium on Biomedical Imaging (ISBI 2012). IEEE, 2012. http://dx.doi.org/10.1109/isbi.2012.6235700.
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Revesz, Tamas, and Tammaryn Lashley. "Pathological aspects of neurodegenerative dementias." In Rijeka Forum on Neurodegenerative Diseases (2 ; 2018 ; Rijeka). Hrvatska akademija znanosti i umjetnosti, 2019. http://dx.doi.org/10.21857/y54jofpzlm.
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Sordillo, Laura A., Peter P. Sordillo, Lin Zhang, and Robert R. Alfano. "Tryptophan and kynurenines in neurodegenerative disease." In Bio-Optics: Design and Application. Washington, D.C.: OSA, 2019. http://dx.doi.org/10.1364/boda.2019.jt4a.8.
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Mishra, Sarthak, and Bhargavi K. "An AI Model for Neurodegenerative Diseases." In 2021 International Conference on Computer Communication and Informatics (ICCCI). IEEE, 2021. http://dx.doi.org/10.1109/iccci50826.2021.9402493.
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Karaduman, Tuğçe, and Habibe Kutuk. "Alzheimer's and Huntington as Neurodegenerative Diseases." In 4th International Symposium on Innovative Approaches in Engineering and Natural Sciences. SETSCI, 2019. http://dx.doi.org/10.36287/setsci.4.6.030.
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Sanches, Clara, Juliette Godard, Marc Teichmann, and Antoni Valero-Cabré. "Neurodegenerative language impairments and transcranial stimulation." In 10th International Conference of Experimental Linguistics. ExLing Society, 2019. http://dx.doi.org/10.36505/exling-2019/10/0046/000408.
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Teixeira, Igor de Lima e., Stella de Angelis Trivellato, Igor Oliveira da Fonseca, Danielle Patrícia Borges Margato, Rodrigo Bazan, and Arthur Oscar Schelp. "An Eye of a Tiger cannot see all the true: a case series." In XIII Congresso Paulista de Neurologia. Zeppelini Editorial e Comunicação, 2021. http://dx.doi.org/10.5327/1516-3180.224.
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Background: Multiple System Atrophy is a neurodegenerative disease with parkinsonism, cerebelar ataxia and autonomic failure. Neurodegeneration with Brain Iron Accumulation diseases are neurodegenerative diseases, as the Pantothenate Kinase-Associated Neurodegeneration, with a very distinct pattern on neuroimaging, known as the “Eye of the Tiger Sign”, which is rare in MSA but many studies confirm the role of striatal regions iron accumulation in parkinsonisms. Objective: We describe MSA patients with iron accumulation in striatal regions in neuroimaging. Methods: We report clinical cases from São Paulo State University-Brazil. Results: 62-year-old with 5 years of bradykinesia and stiffness progressing to wheelchair, REM sleep behavioral disorder, no improvement with levodopa, disarthrophonia and choking with gastrostomy after 3 years, associated to syncope episodes. Neurological examination showed blood pressure of 105x80mmHg lying down and 80x60mmHg standing up, severe disarthrophonia, anterocapitis, severe parkinsonism, postural instability and ataxia. Neuroimaging showed the “Eye of the Tiger”, “putaminal rim” and the “hot cross bun” signs. 78-year-old with 1.5 years syncope episodes, slow walking, falls, difficulty moving hands and feet and constipation. No improvement with levodopa. Neurological examination showed blood pressure of 130x80 mmHg lying down and 90x60 mmHg standing up, severe bradykinesia and stiffness, drooling, ataxia and “square-wave jerks”. Neuroimaging showed “Eye of Tiger” and bilateral “putaminal rim” signs and cerebellar atrophy. In both cases were excluded all differential diagnosis. Conclusions: Both cases fulfilled criteria for MSA, with the radiological sign of the “Eye of the Tiger”. We emphasize the importance of knowing this variation of MSA to avoid diagnostic confusion.
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Elden, Rana Hossam, Walid Al-Atabany, and Vidan Fathi Ghoneim. "Gait Rhythm Fluctuations Assessment for Neurodegenerative Patients." In 2018 9th Cairo International Biomedical Engineering Conference (CIBEC). IEEE, 2018. http://dx.doi.org/10.1109/cibec.2018.8641764.
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Lei, Haijun, Yujia Zhao, Yuting Wen, and Baiying Lei. "Adaptive Sparse Learning for Neurodegenerative Disease Classification." In 2017 IEEE International Symposium on Multimedia (ISM). IEEE, 2017. http://dx.doi.org/10.1109/ism.2017.51.
Full textReports on the topic "Neurodegenerative"
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Weiner, Michael W. 4 Tesla MRI for Neurodegenerative Diseases. Fort Belvoir, VA: Defense Technical Information Center, October 2005. http://dx.doi.org/10.21236/ada462064.
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Dr. Miriam Kleinman, Dr Miriam Kleinman. Developing A New Treatment For Neurodegenerative Diseases. Experiment, March 2013. http://dx.doi.org/10.18258/0205.
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Bambrick, Linda L. Neurotrophin Therapy of Neurodegenerative Disorders with Mitochondrial Dysfunction. Fort Belvoir, VA: Defense Technical Information Center, September 2007. http://dx.doi.org/10.21236/ada484192.
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Bambrick, Linda L. Neurotrophin Therapy of Neurodegenerative Disorders with Mitochondrial Dysfunction. Fort Belvoir, VA: Defense Technical Information Center, September 2004. http://dx.doi.org/10.21236/ada434706.
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Ross, G. W. Neurotoxins and Neurodegenerative Disorders in Japanese-American Men Living in Hawaii. Fort Belvoir, VA: Defense Technical Information Center, April 2005. http://dx.doi.org/10.21236/ada435080.
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Janowsky, Jeri. Markers and Time Course of Neurodegenerative Risk With Androgen Deprivation Therapy. Fort Belvoir, VA: Defense Technical Information Center, April 2011. http://dx.doi.org/10.21236/ada548985.
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Browne, Susan E. Bioenergetic Defects and Oxidative Damage in Transgenic Mouse Models of Neurodegenerative Disorders. Fort Belvoir, VA: Defense Technical Information Center, May 2004. http://dx.doi.org/10.21236/ada430585.
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Browne, Susan E. Bioenergetic Defects and Oxidative Damage in Transgenic Mouse Models of Neurodegenerative Disorders. Fort Belvoir, VA: Defense Technical Information Center, May 2003. http://dx.doi.org/10.21236/ada419306.
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Browne, Susan E. Bioenergetic Defects and Oxidative Damage in Transgenic Mouse Models of Neurodegenerative Disorders. Fort Belvoir, VA: Defense Technical Information Center, June 2005. http://dx.doi.org/10.21236/ada460659.
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Millhorn, David E. Signal Transduction and Gene Regulation During Hypoxic Stress: A Potential Role in Neurodegenerative Disease. Fort Belvoir, VA: Defense Technical Information Center, August 2001. http://dx.doi.org/10.21236/ada397765.
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