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Synaptic Function and Dysfunction in Lysosomal Storage Diseases

Lysosomal storage diseases (LSDs) with neurological involvement are inherited genetic diseases of the metabolism characterized by lysosomal dysfunction and the accumulation of undegraded substrates altering glial and neuronal function. Often, patients with neurological manifestations present with da...

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Autores principales: Rebiai, Rima, Givogri, Maria I., Gowrishankar, Swetha, Cologna, Stephania M., Alford, Simon T., Bongarzone, Ernesto R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7978225/
https://www.ncbi.nlm.nih.gov/pubmed/33746713
http://dx.doi.org/10.3389/fncel.2021.619777
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author Rebiai, Rima
Givogri, Maria I.
Gowrishankar, Swetha
Cologna, Stephania M.
Alford, Simon T.
Bongarzone, Ernesto R.
author_facet Rebiai, Rima
Givogri, Maria I.
Gowrishankar, Swetha
Cologna, Stephania M.
Alford, Simon T.
Bongarzone, Ernesto R.
author_sort Rebiai, Rima
collection PubMed
description Lysosomal storage diseases (LSDs) with neurological involvement are inherited genetic diseases of the metabolism characterized by lysosomal dysfunction and the accumulation of undegraded substrates altering glial and neuronal function. Often, patients with neurological manifestations present with damage to the gray and white matter and irreversible neuronal decline. The use of animal models of LSDs has greatly facilitated studying and identifying potential mechanisms of neuronal dysfunction, including alterations in availability and function of synaptic proteins, modifications of membrane structure, deficits in docking, exocytosis, recycling of synaptic vesicles, and inflammation-mediated remodeling of synapses. Although some extrapolations from findings in adult-onset conditions such as Alzheimer’s disease or Parkinson’s disease have been reported, the pathogenetic mechanisms underpinning cognitive deficits in LSDs are still largely unclear. Without being fully inclusive, the goal of this mini-review is to present a discussion on possible mechanisms leading to synaptic dysfunction in LSDs.
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spelling pubmed-79782252021-03-20 Synaptic Function and Dysfunction in Lysosomal Storage Diseases Rebiai, Rima Givogri, Maria I. Gowrishankar, Swetha Cologna, Stephania M. Alford, Simon T. Bongarzone, Ernesto R. Front Cell Neurosci Cellular Neuroscience Lysosomal storage diseases (LSDs) with neurological involvement are inherited genetic diseases of the metabolism characterized by lysosomal dysfunction and the accumulation of undegraded substrates altering glial and neuronal function. Often, patients with neurological manifestations present with damage to the gray and white matter and irreversible neuronal decline. The use of animal models of LSDs has greatly facilitated studying and identifying potential mechanisms of neuronal dysfunction, including alterations in availability and function of synaptic proteins, modifications of membrane structure, deficits in docking, exocytosis, recycling of synaptic vesicles, and inflammation-mediated remodeling of synapses. Although some extrapolations from findings in adult-onset conditions such as Alzheimer’s disease or Parkinson’s disease have been reported, the pathogenetic mechanisms underpinning cognitive deficits in LSDs are still largely unclear. Without being fully inclusive, the goal of this mini-review is to present a discussion on possible mechanisms leading to synaptic dysfunction in LSDs. Frontiers Media S.A. 2021-03-04 /pmc/articles/PMC7978225/ /pubmed/33746713 http://dx.doi.org/10.3389/fncel.2021.619777 Text en Copyright © 2021 Rebiai, Givogri, Gowrishankar, Cologna, Alford and Bongarzone. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cellular Neuroscience
Rebiai, Rima
Givogri, Maria I.
Gowrishankar, Swetha
Cologna, Stephania M.
Alford, Simon T.
Bongarzone, Ernesto R.
Synaptic Function and Dysfunction in Lysosomal Storage Diseases
title Synaptic Function and Dysfunction in Lysosomal Storage Diseases
title_full Synaptic Function and Dysfunction in Lysosomal Storage Diseases
title_fullStr Synaptic Function and Dysfunction in Lysosomal Storage Diseases
title_full_unstemmed Synaptic Function and Dysfunction in Lysosomal Storage Diseases
title_short Synaptic Function and Dysfunction in Lysosomal Storage Diseases
title_sort synaptic function and dysfunction in lysosomal storage diseases
topic Cellular Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7978225/
https://www.ncbi.nlm.nih.gov/pubmed/33746713
http://dx.doi.org/10.3389/fncel.2021.619777
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