Abstract | BACKGROUND:
Rotenone is an environmental neurotoxin that induces accumulation of α- synuclein and degeneration of dopaminergic neurons in substantia nigra pars compacta (SNpc), but the molecular mechanisms are not fully understood. We investigated whether rotenone induced impairment of autophagic flux and lysosomal functions. METHODS: Autophagy flux, accumulation of α- synuclein, lysosomal membrane integrity and neurodegeneration were assessed in the rotenone-treated rat model and PC12 cells, and the effects of the autophagy inducer trehalose on rotenone's cytotoxicity were also studied. RESULTS: CONCLUSIONS: These studies indicate that the lysosomal dysfunction contributes to rotenone's neurotoxicity and restoration of lysosomal function could be a new therapeutic strategy for Parkinson's disease.
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Authors | F Wu, H-D Xu, J-J Guan, Y-S Hou, J-H Gu, X-C Zhen, Z-H Qin |
Journal | Neuroscience
(Neuroscience)
Vol. 284
Pg. 900-911
(Jan 22 2015)
ISSN: 1873-7544 [Electronic] United States |
PMID | 25446361
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved. |
Chemical References |
- Antiparkinson Agents
- Snca protein, rat
- alpha-Synuclein
- Rotenone
- Trehalose
- Tyrosine 3-Monooxygenase
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Topics |
- Animals
- Antiparkinson Agents
(pharmacology)
- Autophagy
(drug effects, physiology)
- Lysosomes
(drug effects, metabolism)
- Male
- PC12 Cells
- Parkinsonian Disorders
(drug therapy, physiopathology)
- Pars Compacta
(drug effects, physiopathology)
- Random Allocation
- Rats
- Rats, Inbred Lew
- Rotenone
(toxicity)
- Trehalose
(pharmacology)
- Tyrosine 3-Monooxygenase
(metabolism)
- alpha-Synuclein
(metabolism)
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