Role of chaperone-mediated autophagy in degrading Huntington's disease-associated huntingtin protein.

Abstract:

:Mutant N-terminal huntingtin (Htt) protein resulting from Huntington's disease (HD) with expanded polyglutamine accumulates and forms aggregates in vulnerable neurons. Both ubiquitin proteasomal and autophagic pathways contribute to the degradation of mutant Htt. Here, we focus on the involvement of chaperone-mediated autophagy (CMA), a selective form of autophagy in the clearance of Htt. Selective catabolism in CMA is conferred by the presence of a KFERQ-like targeting motif in the substrates, by which molecular chaperones recognize the hydrophobic surfaces of the misfolded substrates, and transfer them to the lysosomal membrane protein type-2A, LAMP-2A. The substrates are taken into the lysosomes through LAMP-2A and are rapidly degraded by the lysosomal enzymes. Taken together, we summarize the recent evidence to elucidate that Htt is also a potential substrate of CMA. We propose that the manipulation of CMA could be a therapeutic strategy for HD.

authors

Qi L,Zhang XD

doi

10.1093/abbs/gmt133

subject

Has Abstract

pub_date

2014-02-01 00:00:00

pages

83-91

issue

2

eissn

1672-9145

issn

1745-7270

pii

gmt133

journal_volume

46

pub_type

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