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ID 48732
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creator
Sakamoto, Shuichiro
Miyara, Masatsugu
Sanoh, Seigo
abstract
Parkinson’s disease (PD) is a prevalent neurodegenerative disorder, mainly characterised by the progressive loss of dopaminergic neurons. MPP+ has been widely used as a PD-related neurotoxin, and their reports suggested the several hypotheses for neuronal cell death. However, most of these hypotheses come from the studies about the acute MPP+ exposure. We previously revealed that mild MPP+ exposure (10 and 200 μM), which induces gradual cell death, impairs autophagosome degradation at 48 h. In the present study, we further investigated the specific events of mild MPP+ exposure and revealed that mild MPP+ exposure causes the cell death through glucose starvation, but not acute toxic model (2.5 and 5 mM). At 36 h after mild MPP+ exposure, autophagosome synthesis was enhanced owing to glucose starvation and continued to enhance until 48 h, despite impaired autophagosome degradation. Inhibition of autophagosome synthesis reduced mild MPP+-induced cell death. In conclusion, we clarified that glucose starvation-enhanced autophagosome synthesis occurs at an earlier stage than impaired autophagosome degradation and is important in mild MPP+ toxicity.
description
This work was supported by Japan Society for the Promotion of Science (JSPS) Grants-in-Aid for Scientific Research (B) Grant Number 24406004 (to Y.K.), The Pharmacological Research Foundation, Tokyo, Japan (to Y.K.), and Suzuken Memorial Foundation (to Y.K.).
journal title
Scientific Reports
volume
Volume 7
start page
46668
date of issued
2017-04-26
publisher
Nature Research
issn
2045-2322
publisher doi
language
eng
nii type
Journal Article
HU type
Journal Articles
DCMI type
text
format
application/pdf
text version
publisher
rights
© The Author(s) 2017. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
relation url
department
Graduate School of Biomedical & Health Sciences