期刊
JOURNAL OF NEUROCHEMISTRY
卷 117, 期 1, 页码 112-120出版社
WILEY
DOI: 10.1111/j.1471-4159.2011.07180.x
关键词
HDAC6; alpha-synuclein; aggresome; autophagy; MPP; Parkinson's disease
资金
- National Natural Science Foundation of China [30870869]
- Major State Basic Research Development Program of China (973 Program) [2011CB510003]
P>Increasing evidence suggests that the ubiquitin-binding histone deacetylase-6 (HDAC6) plays an important role in the clearance of misfolded proteins by autophagy. In this study, we treated PC-12 cells over-expressing human mutant (A53T) alpha-synuclein (alpha-syn) and SH-SY5Y cells with MPP+. It was found that HDAC6 expression significantly increased and mainly colocalized with alpha-syn in the perinuclear region to form aggresome-like bodies. HDAC6 deficiency blocked the formation of aggresome-like bodies and interfered with the autophagy in response to MPP+-induced stress. Moreover, misfolded alpha-syn accumulated into the nuclei, resulting in its reduced clearance, and finally, the number of apoptotic cells significantly increased. Taken together, HDAC6 participated in the degradation of MPP+-induced misfolded alpha-syn aggregates by regulating the aggresome-autophagy pathway. Understanding the mechanism may disclose potential therapeutic targets for synucleinopathies such as Parkinson's disease.
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