机构：[1]Department of Neurology, Second Affiliated Hospital of Soochow University, Suzhou, China[2]Institute of Neuroscience, Soochow University, Suzhou, China
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.
基金：
This work was supported by grants 30870869 from the National Natural Science Foundation of China and a grant from the Major State Basic Research Development Program of China (973 Program, No. 2011CB510003).
通讯机构：[*]Institute of Neuroscience, Soochow University, 199 Ren-Ai Road, Suzhou City, Jiangsu Province 215123, China.
推荐引用方式(GB/T 7714)：
Su Min,Shi Ji-Jun,Yang Ya-Ping,et al.HDAC6 regulates aggresome-autophagy degradation pathway of alpha-synuclein in response to MPP plus -induced stress[J].JOURNAL OF NEUROCHEMISTRY.2011,117(1):112-20.doi:10.1111/j.1471-4159.2011.07180.x.
APA：
Su, Min,Shi, Ji-Jun,Yang, Ya-Ping,Li, Jun,Zhang, Yan-Ling...&Liu, Chun-Feng.(2011).HDAC6 regulates aggresome-autophagy degradation pathway of alpha-synuclein in response to MPP plus -induced stress.JOURNAL OF NEUROCHEMISTRY,117,(1)
MLA：
Su, Min,et al."HDAC6 regulates aggresome-autophagy degradation pathway of alpha-synuclein in response to MPP plus -induced stress".JOURNAL OF NEUROCHEMISTRY 117..1(2011):112-20
医学