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HDAC6 regulates aggresome‐autophagy degradation pathway of α‐synuclein in response to MPP + ‐induced stress
Author(s) -
Su Min,
Shi JiJun,
Yang YaPing,
Li Jun,
Zhang YanLing,
Chen Jin,
Hu LiFang,
Liu ChunFeng
Publication year - 2011
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2011.07180.x
Subject(s) - aggresome , hdac6 , autophagy , microbiology and biotechnology , protein aggregation , ubiquitin , chemistry , synucleinopathies , biology , histone deacetylase , parkinson's disease , alpha synuclein , apoptosis , histone , biochemistry , medicine , disease , gene
J. Neurochem. (2011) 117 , 112–120. Abstract 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) α‐synuclein (α‐syn) and SH‐SY5Y cells with MPP + . It was found that HDAC6 expression significantly increased and mainly colocalized with α‐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 α‐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 α‐syn aggregates by regulating the aggresome‐autophagy pathway. Understanding the mechanism may disclose potential therapeutic targets for synucleinopathies such as Parkinson’s disease.