HDAC6 regulates aggresome-autophagy degradation pathway of α-synuclein in response to MPP+-induced s

• 作 者: Min SU Ji-Jun SHI Ya-Ping YANG Jun LI Yan-Ling ZHANG Jin CHEN Li-Fang HU Chun-Feng LIU
• 机 构: Department of Neurology, Second Affiliated Hospital of Soochow University, Suzhou, China;Institute o
• 出 处: 中国神经科学学会第九届全国学术会议暨第五届会员代表大会
• 发表日期: 2011年1期
• 关键词: HDAC6 α-synuclein aggresome autophagy MPP+ Parkinson disease

　　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 overexpressing 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 disease.