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Proteolysis by the ubiquitin-proteasome pathway (UPP) in the nervous system has been extensively studied both in the context of normal physiological function as well as abnormal pathological conditions. Although ubiquitin was used as a marker of brain pathology, the normal functions of the UPP were not studied much in the nervous system until the 1990s. The early investigations focused on synaptic plasticity which was followed by studies on the roles of protein degradation in the development of the nervous system. Research on the role of abnormal roles of the UPP follows a parallel trajectory. Since the 2000s, the field has grown to encompass many subareas of research and several model systems. Despite the progress made, many unanswered questions still remain. For example, there are many unknowns about the precise spatial and temporal control of protein degradation in the normal nervous system. With respect to the roles of proteolysis in brain pathology a major challenge is to elucidate the connection between impaired protein degradation and disease progression. In addition, in-depth studies of the roles of ubiquitin-proteasome-mediated proteolysis in neurodegenerative diseases are promising in identifying therapeutic targets. This ebook contains original research papers and insightful reviews that cover several aspects of proteolysis by the UPP and its physiological as well as pathological functions in the nervous system.
proteasome --- deubiquitinating --- glutamate receptors --- synaptic plasticity --- memory --- aging --- neurodegenerative --- Alzheimer's disease --- Huntington's disease --- neuroinflammation
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The prevalence of neurodegenerative disorders is increasing dramatically and one of the major challenges today is the need of early and accurate diagnosis, the other is the need of more effective therapies -in turn the development of such therapies also requires early and accurate diagnosis-. The main hope for an earlier and more accurate diagnosis comes from the use of biomarkers. Much research is being done trying to solve the many interrogates related to the role of biomarkers in clinical practice, including the early diagnosis, differential diagnosis and follow-up of neurodegenerative disorders. This is a field where translational research is intense enough to make this topic interesting for basic researchers and clinicians. Indeed, the amount and quality of articles received in response to the call for contributions was very good. This eBook contains a good amount of high quality articles devoted to diverse techniques across several neurodegenerative disorders from different perspectives, including original reports, reviews, methods reports and opinion letters on biochemical biomarkers in biological fluids, neuroimaging techniques and multidimensional approaches linking clinical findings with biomarkers. The disorders covered are also diverse: Alzheimer’s disease, Frontotemporal Dementia, Dementia with Lewy Bodies, Huntington’s disease, Parkinson’s disease among others. As we can learn from articles in this Research Topic, biomarkers are allowing us to expand the knowledge on the biological and anatomical basis of neurodegenerative diseases and to implement diagnostic techniques in clinical practice and clinical trials.
biomarker --- MTAi --- neurodegenerative disease --- Neurodegenerative Diseases --- Parkinson's disease --- Huntington's disease --- Frontotemporal dementia (FTD) --- CSF biomarkers
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Innovations in molecular biology are allowing neuroscientists to study the brain with unprecedented resolution, from the level of single molecules to integrated gene circuits. Chief among these innovations is the CRISPR-Cas genome editing technology, which has the precision and scalability to tackle the complexity of the brain. This Colloque Médecine et Recherche has brought together experts from around the world that are applying genome editing to address important challenges in neuroscience, including basic biology in model organisms that has the power to reveal systems-level insight into how the nervous system develops and functions as well as research focused on understanding and treating human neurological disorders.
CRISPR --- genetic engineering --- DNA --- double-strand breaks --- Parkinson's disease --- Huntington's disease --- Rett syndrome --- muscular dystrophy
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The basal ganglia constitute a group of subcortical structures, highly interconnected among themselves, as well as with the cerebral cortex, thalamus and other brain areas. These nuclei play a central role in the control of voluntary movement, and their specific pathology comprises the group of diseases known as movement disorders, including Parkinson's disease, Huntington's disease, dystonia and Gilles de la Tourette syndrome, among others. Additionally, the presence of a number of circuits within the basal ganglia related to non-motor functions has been acknowledged. Currently, the basal ganglia are thought to participate in cognitive, limbic and learning functions. Moreover, disorders related to the basal ganglia are known to involve a number of complex, non-motor symptoms and syndromes (e.g. compulsive and addictive behavior). In the light of this evidence, it is becoming clear that our knowledge about the basal ganglia needs to be revised, and that new pathophysiological models of movement disorders are needed. In this context, the study of the pathophysiology of the basal ganglia and the treatment of their pathology is becoming increasingly interdisciplinary. Nowadays, an appropriate approach to the study of these problems must necessarily involve the use of complex mathematical modeling, computer simulations, basic research (ranging from biomolecular studies to animal experimentation), and clinical research. This research topic aims to bring together the most recent advances related to the pathophysiology of the basal ganglia and movement disorders.
basal ganglia --- deep brain stimulation --- non-motor symptoms --- movement disorders --- computational modeling --- Parkinson's disease --- Huntington's disease --- Braak's hypothesis --- nonlinear dynamics --- cycling
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