表观遗传因素是导致帕金森病(PD)发生的重要原因。前期研究发现PD患者中脑黑质小胶质细胞中组蛋白去乙酰化酶HDAC2表达增加。α-synuclein（α-syn）纤维原刺激小胶质细胞或α-syn过表达人神经母细胞瘤系SH-SY5Y致HDAC2表达升高，推测α-syn可能是引起HDAC2表达增加的因素。致炎作用是α-syn的主要致病机制之一，那么HDAC2有可能通过对转录因子的赖氨酸残基去乙酰化致其激活或与转录因子形成复合物而促进炎性基因表达，进而在α-syn致炎性反应中发挥作用。本项目将探索α-syn在转录水平调控HDAC2表达的机制，明确HDAC2如何通过对相关转录因子的去乙酰化修饰或与其形成复合物促进炎性因子的异常表达，进而参与α-syn的致病机制。

Epigenetic modifications play important roles in pathogenesis of Parkinson's disease(PD). Our preliminary data showed Histone deacetylase-2(HDAC2) increased in microglia of substantia nigra of PD patients. HDAC2 expression was enhanced by α-synuclein fibrils or α-synuclein overexpression. Neuroinflammation is one major pathogenetic mechaism of α-synuclein. HDAC2 could deacetylate lysine residues of transcription factors, or form complex with transcription factors, and promote gene expression. We hypothesize that HDAC2 might aggravate neuroinflammation by activating transcription factors and promoting inflammatory factors expression. Thus, this project will explore 1) the mechanism that α-synuclein regulate HDAC2 expression ; 2) the inflammatory factors whose expression might be regulated by HDAC2, and the transcription factors whose activation or deactivation might be HDAC2-dependent; 3) explore the neuroprotective function of HDAC2 inhibitor in α-synuclein PD model.