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VPS35, the Retromer Complex and Parkinson’s Disease

Mutations in the vacuolar protein sorting 35 ortholog (VPS35) gene encoding a core component of the retromer complex, have recently emerged as a new cause of late-onset, autosomal dominant familial Parkinson’s disease (PD). A single missense mutation, AspD620Asn (D620N), has so far been unambiguousl...

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Autores principales: Williams, Erin T., Chen, Xi, Moore, Darren J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: IOS Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5438477/
https://www.ncbi.nlm.nih.gov/pubmed/28222538
http://dx.doi.org/10.3233/JPD-161020
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author Williams, Erin T.
Chen, Xi
Moore, Darren J.
author_facet Williams, Erin T.
Chen, Xi
Moore, Darren J.
author_sort Williams, Erin T.
collection PubMed
description Mutations in the vacuolar protein sorting 35 ortholog (VPS35) gene encoding a core component of the retromer complex, have recently emerged as a new cause of late-onset, autosomal dominant familial Parkinson’s disease (PD). A single missense mutation, AspD620Asn (D620N), has so far been unambiguously identified to cause PD in multiple individuals and families worldwide. The exact molecular mechanism(s) by which VPS35 mutations induce progressive neurodegeneration in PD are not yet known. Understanding these mechanisms, as well as the perturbed cellular pathways downstream of mutant VPS35, is important for the development of appropriate therapeutic strategies. In this review, we focus on the current knowledge surrounding VPS35 and its role in PD. We provide a critical discussion of the emerging data regarding the mechanisms underlying mutant VPS35-mediated neurodegeneration gleaned from genetic cell and animal models and highlight recent advances that may provide insight into the interplay between VPS35 and several other PD-linked gene products (i.e. α-synuclein, LRRK2 and parkin) in PD. Present data support a role for perturbed VPS35 and retromer function in the pathogenesis of PD.
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spelling pubmed-54384772017-05-30 VPS35, the Retromer Complex and Parkinson’s Disease Williams, Erin T. Chen, Xi Moore, Darren J. J Parkinsons Dis Review Mutations in the vacuolar protein sorting 35 ortholog (VPS35) gene encoding a core component of the retromer complex, have recently emerged as a new cause of late-onset, autosomal dominant familial Parkinson’s disease (PD). A single missense mutation, AspD620Asn (D620N), has so far been unambiguously identified to cause PD in multiple individuals and families worldwide. The exact molecular mechanism(s) by which VPS35 mutations induce progressive neurodegeneration in PD are not yet known. Understanding these mechanisms, as well as the perturbed cellular pathways downstream of mutant VPS35, is important for the development of appropriate therapeutic strategies. In this review, we focus on the current knowledge surrounding VPS35 and its role in PD. We provide a critical discussion of the emerging data regarding the mechanisms underlying mutant VPS35-mediated neurodegeneration gleaned from genetic cell and animal models and highlight recent advances that may provide insight into the interplay between VPS35 and several other PD-linked gene products (i.e. α-synuclein, LRRK2 and parkin) in PD. Present data support a role for perturbed VPS35 and retromer function in the pathogenesis of PD. IOS Press 2017-05-16 /pmc/articles/PMC5438477/ /pubmed/28222538 http://dx.doi.org/10.3233/JPD-161020 Text en IOS Press and the authors. All rights reserved https://creativecommons.org/licenses/by-nc/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial (CC BY-NC 4.0) License (https://creativecommons.org/licenses/by-nc/4.0/) , which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review
Williams, Erin T.
Chen, Xi
Moore, Darren J.
VPS35, the Retromer Complex and Parkinson’s Disease
title VPS35, the Retromer Complex and Parkinson’s Disease
title_full VPS35, the Retromer Complex and Parkinson’s Disease
title_fullStr VPS35, the Retromer Complex and Parkinson’s Disease
title_full_unstemmed VPS35, the Retromer Complex and Parkinson’s Disease
title_short VPS35, the Retromer Complex and Parkinson’s Disease
title_sort vps35, the retromer complex and parkinson’s disease
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5438477/
https://www.ncbi.nlm.nih.gov/pubmed/28222538
http://dx.doi.org/10.3233/JPD-161020
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