Pathogenic Mutation in VPS35 Impairs Its Protection against MPP+ Cytotoxicity

Pathogenic Mutation in VPS35 Impairs Its Protection against MPP+ Cytotoxicity

Parkinson's disease primarily results from progressive degeneration of dopaminergic neurons in the substantia nigra. Both neuronal toxicants and genetic factors are suggested to be involved in the disease pathogenesis. The mitochondrial toxicant 1-methyl-4-phenylpyridinium (MPP+) shows a highly...

Full description

Bibliographic Details
Main Authors: Bi, Fangfang, Li, Fang, Huang, Cao, Zhou, Hongxia
Format: Online
Language:English
Published: Ivyspring International Publisher 2013
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3572397/
id pubmed-3572397
recordtype oai_dc
spelling pubmed-35723972013-02-14 Pathogenic Mutation in VPS35 Impairs Its Protection against MPP+ Cytotoxicity Bi, Fangfang Li, Fang Huang, Cao Zhou, Hongxia Research Paper Parkinson's disease primarily results from progressive degeneration of dopaminergic neurons in the substantia nigra. Both neuronal toxicants and genetic factors are suggested to be involved in the disease pathogenesis. The mitochondrial toxicant 1-methyl-4-phenylpyridinium (MPP+) shows a highly selective toxicity to dopaminergic neurons. Recent studies indicate that mutation in the vacuolar protein sorting 35 (vps35) gene segregates with Parkinson's disease in some families, but how mutation in the vps35 gene causes dopaminergic cell death is not known. Here, we report that enhanced VPS35 expression protected dopaminergic cells against MPP+ toxicity and that this neuroprotection was compromised by pathogenic mutation in the gene. A loss of neuroprotective functions contributes to the pathogenesis of VPS35 mutation in Parkinson's disease. Ivyspring International Publisher 2013-01-26 /pmc/articles/PMC3572397/ /pubmed/23411763 http://dx.doi.org/10.7150/ijbs.5617 Text en © Ivyspring International Publisher. This is an open-access article distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Bi, Fangfang
Li, Fang
Huang, Cao
Zhou, Hongxia
spellingShingle Bi, Fangfang
Li, Fang
Huang, Cao
Zhou, Hongxia
Pathogenic Mutation in VPS35 Impairs Its Protection against MPP+ Cytotoxicity
author_facet Bi, Fangfang
Li, Fang
Huang, Cao
Zhou, Hongxia
author_sort Bi, Fangfang
title Pathogenic Mutation in VPS35 Impairs Its Protection against MPP+ Cytotoxicity
title_short Pathogenic Mutation in VPS35 Impairs Its Protection against MPP+ Cytotoxicity
title_full Pathogenic Mutation in VPS35 Impairs Its Protection against MPP+ Cytotoxicity
title_fullStr Pathogenic Mutation in VPS35 Impairs Its Protection against MPP+ Cytotoxicity
title_full_unstemmed Pathogenic Mutation in VPS35 Impairs Its Protection against MPP+ Cytotoxicity
title_sort pathogenic mutation in vps35 impairs its protection against mpp+ cytotoxicity
description Parkinson's disease primarily results from progressive degeneration of dopaminergic neurons in the substantia nigra. Both neuronal toxicants and genetic factors are suggested to be involved in the disease pathogenesis. The mitochondrial toxicant 1-methyl-4-phenylpyridinium (MPP+) shows a highly selective toxicity to dopaminergic neurons. Recent studies indicate that mutation in the vacuolar protein sorting 35 (vps35) gene segregates with Parkinson's disease in some families, but how mutation in the vps35 gene causes dopaminergic cell death is not known. Here, we report that enhanced VPS35 expression protected dopaminergic cells against MPP+ toxicity and that this neuroprotection was compromised by pathogenic mutation in the gene. A loss of neuroprotective functions contributes to the pathogenesis of VPS35 mutation in Parkinson's disease.
publisher Ivyspring International Publisher
publishDate 2013
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3572397/
_version_ 1611954890926456832

Similar Items