Is Alpha-Synuclein Loss-of-Function a Contributor to Parkinsonian Pathology? Evidence from Non-human Primates

Accumulation of alpha-synuclein (α-syn) in Lewy bodies and neurites of midbrain dopamine neurons is diagnostic for Parkinson's disease (PD), leading to the proposal that PD is a toxic gain-of-function synucleinopathy. Here we discuss the alternative viewpoint that α-syn displacement from synaps...

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Autores principales: Collier, Timothy J., Redmond, D. Eugene, Steece-Collier, Kathy, Lipton, Jack W., Manfredsson, Fredric P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2016
Materias:
Psychiatry
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4731516/
https://www.ncbi.nlm.nih.gov/pubmed/26858591
http://dx.doi.org/10.3389/fnins.2016.00012
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author Collier, Timothy J.
Redmond, D. Eugene
Steece-Collier, Kathy
Lipton, Jack W.
Manfredsson, Fredric P.
author_facet Collier, Timothy J.
Redmond, D. Eugene
Steece-Collier, Kathy
Lipton, Jack W.
Manfredsson, Fredric P.
author_sort Collier, Timothy J.
collection PubMed
description Accumulation of alpha-synuclein (α-syn) in Lewy bodies and neurites of midbrain dopamine neurons is diagnostic for Parkinson's disease (PD), leading to the proposal that PD is a toxic gain-of-function synucleinopathy. Here we discuss the alternative viewpoint that α-syn displacement from synapses by misfolding and aggregation results in a toxic loss-of-function. In support of this hypothesis we provide evidence from our pilot study demonstrating that knockdown of endogenous α-syn in dopamine neurons of non-human primates reproduces the pattern of nigrostriatal degeneration characteristic of PD.
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spelling pubmed-47315162016-02-08 Is Alpha-Synuclein Loss-of-Function a Contributor to Parkinsonian Pathology? Evidence from Non-human Primates Collier, Timothy J. Redmond, D. Eugene Steece-Collier, Kathy Lipton, Jack W. Manfredsson, Fredric P. Front Neurosci Psychiatry Accumulation of alpha-synuclein (α-syn) in Lewy bodies and neurites of midbrain dopamine neurons is diagnostic for Parkinson's disease (PD), leading to the proposal that PD is a toxic gain-of-function synucleinopathy. Here we discuss the alternative viewpoint that α-syn displacement from synapses by misfolding and aggregation results in a toxic loss-of-function. In support of this hypothesis we provide evidence from our pilot study demonstrating that knockdown of endogenous α-syn in dopamine neurons of non-human primates reproduces the pattern of nigrostriatal degeneration characteristic of PD. Frontiers Media S.A. 2016-01-29 /pmc/articles/PMC4731516/ /pubmed/26858591 http://dx.doi.org/10.3389/fnins.2016.00012 Text en Copyright © 2016 Collier, Redmond, Steece-Collier, Lipton and Manfredsson. 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) or licensor 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 Psychiatry
Collier, Timothy J.
Redmond, D. Eugene
Steece-Collier, Kathy
Lipton, Jack W.
Manfredsson, Fredric P.
Is Alpha-Synuclein Loss-of-Function a Contributor to Parkinsonian Pathology? Evidence from Non-human Primates
title Is Alpha-Synuclein Loss-of-Function a Contributor to Parkinsonian Pathology? Evidence from Non-human Primates
title_full Is Alpha-Synuclein Loss-of-Function a Contributor to Parkinsonian Pathology? Evidence from Non-human Primates
title_fullStr Is Alpha-Synuclein Loss-of-Function a Contributor to Parkinsonian Pathology? Evidence from Non-human Primates
title_full_unstemmed Is Alpha-Synuclein Loss-of-Function a Contributor to Parkinsonian Pathology? Evidence from Non-human Primates
title_short Is Alpha-Synuclein Loss-of-Function a Contributor to Parkinsonian Pathology? Evidence from Non-human Primates
title_sort is alpha-synuclein loss-of-function a contributor to parkinsonian pathology? evidence from non-human primates
topic Psychiatry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4731516/
https://www.ncbi.nlm.nih.gov/pubmed/26858591
http://dx.doi.org/10.3389/fnins.2016.00012
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