The Role of Chaperone-mediated Autophagy in Neurotoxicity Induced by Alpha-synuclein After Methamphetamine Exposure

Overview

Journal Brain Behav

Specialty Psychology

Date 2019 Jul 10

PMID 31286692

Citations 14

Authors

Leping Sun

Yongling Lian

Jiuyang Ding

Yunle Meng

Chen Li

Ling Chen

Pingming Qiu

Affiliations

Soon will be listed here.

Abstract

Introduction: Chaperone-mediated autophagy (CMA) is an autophagy-lysosome pathway (ALP) that is different from the other two lysosomal pathways, namely, macroautophagy and microautophagy, and can selectively degrade cytosolic proteins in lysosomes without vesicle formation. CMA activity declines in neurodegenerative diseases such as Parkinson's disease, and similar neurotoxicity can occur after methamphetamine (METH) treatment. The relationship between CMA and METH-induced neurotoxicity is not clear.

Methods: We detected changes in the chaperone protein Hsc70 and the lysosomal surface receptor Lamp-2a after METH treatment and then regulated these two proteins by small interfering RNA and DNA plasmid transfection to investigate how CMA influences METH-induced neurotoxicity.

Results: We found that CMA activity is decreased after METH exposure in neurons and downregulated Lamp-2a can aggravate the neurotoxicity induced by α-Syn after METH exposure and that Hsc70 overexpression can relieve the abnormal levels of alpha-synuclein and its aggregate forms and the increase in cell apoptosis induced by METH.

Conclusions: The results provide in vivo evidence for CMA plays a pivotal role in METH-induced neurotoxicity, and upregulation of Hsc70 expression significantly protects neuronal cells against METH-induced toxicity. This research may pave the way for potential therapeutic approaches targeting CMA for METH abuse and neurodegenerative disorders.

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The Common Denominators of Parkinson's Disease Pathogenesis and Methamphetamine Abuse.

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