Alpha-synuclein and Parkinson disease

OBJECTIVE:To review the recent progresses on the studies ofα-synuclein in the pathogenesis of Parkinson disease(PD)and look into the perspective ofα-synuclein as a new therapy target.DATA SOURCES:To search the literatures on the progresses of PD studies,especially on the structure,gene expression of α-synuclein and the pathogenesis of PD in Medline from January 1998 to February 2007.Search terms were “Parkinson’s disease,α-synuclein” in English.STUDY SELECTION:Initial check the data and choose the original and review articles directly linked to the role of α-synuclein in PD pathogenesis and screening out indirectly discussing articles.Collect the full text and trace the quoting articles and the quoted articles.Only the latest reviews were chosen in Chinese articles.DATA EXTRACTION:There were 424 articles on α-synuclein and its role in the pathogenesis of PD and 43 articles directly related withα-synuclein were chosen among which 12 were reviews.DATA SYNTHESIS:α-synuclein is a kind of soluble protein expressed in pre-synapse in central nervous system encoded by gene in homologous chromosome 4q21.It has physiological function in modulating the stability of membrane and neural plasticity.There is a close relationship between gene mutation inα-synuclein and the pathogenesis of PD.Environmental and genetic factors can induce the misfolding ofα-synuclein,and secondary structural change can result in oligomer formation which induces a series of cascade reaction to damage dopaminergic system subsequently.Cell and animal transgenic and non-transgenic models are established recently and the important role of α-synuclein in the pathogenesis both of familial and sporadic PD is confirmed.Studies reveal that inhibiting the aggregation of α-synuclein can prevent its neurotoxicity;gene parkin can intercept the cell death pathway triggered by the aggregation ofα-synuclein in cytoplasm.CONCLUSION:Gene mutation ofα-synuclein and the impairment in its structure and function are importan in the pathogenesis of PD.Intervention of the gene mutations and abnormal protein aggregation ofα-synuclein may be a new strategy for preventing and treating PD.