PMID- 31286692
OWN - NLM
STAT- MEDLINE
DCOM- 20200501
LR  - 20210110
IS  - 2162-3279 (Electronic)
VI  - 9
IP  - 8
DP  - 2019 Aug
TI  - The role of chaperone-mediated autophagy in neurotoxicity induced by 
      alpha-synuclein after methamphetamine exposure.
PG  - e01352
LID - 10.1002/brb3.1352 [doi]
LID - e01352
AB  - 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 alpha-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.
CI  - (c) 2019 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.
FAU - Sun, Leping
AU  - Sun L
AD  - School of Forensic Medicine, Southern Medical University, Guangzhou, China.
FAU - Lian, Yongling
AU  - Lian Y
AD  - School of Forensic Medicine, Southern Medical University, Guangzhou, China.
FAU - Ding, Jiuyang
AU  - Ding J
AD  - School of Forensic Medicine, Southern Medical University, Guangzhou, China.
AD  - Department of Anatomy, Zunyi Medical College, Zunyi, China.
FAU - Meng, Yunle
AU  - Meng Y
AD  - School of Forensic Medicine, Southern Medical University, Guangzhou, China.
FAU - Li, Chen
AU  - Li C
AD  - School of Forensic Medicine, Southern Medical University, Guangzhou, China.
FAU - Chen, Ling
AU  - Chen L
AUID- ORCID: 0000-0001-7699-4820
AD  - School of Forensic Medicine, Southern Medical University, Guangzhou, China.
FAU - Qiu, Pingming
AU  - Qiu P
AUID- ORCID: 0000-0002-5579-1124
AD  - School of Forensic Medicine, Southern Medical University, Guangzhou, China.
LA  - eng
SI  - figshare/10.6084/m9.figshare.8166029
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190709
PL  - United States
TA  - Brain Behav
JT  - Brain and behavior
JID - 101570837
RN  - 0 (Central Nervous System Stimulants)
RN  - 0 (HSC70 Heat-Shock Proteins)
RN  - 0 (HSPA8 protein, human)
RN  - 0 (LAMP2 protein, human)
RN  - 0 (Lysosomal-Associated Membrane Protein 2)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (alpha-Synuclein)
RN  - 44RAL3456C (Methamphetamine)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Central Nervous System Stimulants/toxicity
MH  - *Chaperone-Mediated Autophagy
MH  - Down-Regulation
MH  - HSC70 Heat-Shock Proteins/*metabolism
MH  - Humans
MH  - Lysosomal-Associated Membrane Protein 2/*metabolism
MH  - Methamphetamine/*toxicity
MH  - *Neurons/drug effects/metabolism
MH  - *Neurotoxicity Syndromes/etiology/metabolism/prevention & control
MH  - Protective Factors
MH  - RNA, Small Interfering
MH  - Rats
MH  - alpha-Synuclein/*metabolism
PMC - PMC6710200
OTO - NOTNLM
OT  - alpha-synuclein
OT  - chaperone-mediated autophagy
OT  - methamphetamine
OT  - neurotoxicity
EDAT- 2019/07/10 06:00
MHDA- 2020/05/02 06:00
PMCR- 2019/07/09
CRDT- 2019/07/10 06:00
PHST- 2018/12/05 00:00 [received]
PHST- 2019/05/28 00:00 [revised]
PHST- 2019/06/02 00:00 [accepted]
PHST- 2019/07/10 06:00 [pubmed]
PHST- 2020/05/02 06:00 [medline]
PHST- 2019/07/10 06:00 [entrez]
PHST- 2019/07/09 00:00 [pmc-release]
AID - BRB31352 [pii]
AID - 10.1002/brb3.1352 [doi]
PST - ppublish
SO  - Brain Behav. 2019 Aug;9(8):e01352. doi: 10.1002/brb3.1352. Epub 2019 Jul 9.