Structural polymorphism of pathological amyloid fibrils of α-syn in Parkinson's disease

【摘要】：Abnormal aggregation of amyloid proteins is the key pathological event occurring in different Neurodegenerative diseases(ND).Numerous evidences have shown that the structural diversity,so-called polymorphism,is decisive to the amyloid pathology and is closely associated with the onset,progression,and phenotype of ND.But how could one protein form so many stable structures?In this talk,I will introduce our recent studies on amyloid aggregation of α-synuclein(α-syn) which is closely associated with Parkinson's disease(PD).Our works reveal that different factors including familial mutations,post-translational modifications,and noncovalent cofactor may induce the formation of amyloid fibrils with a high variety of different structures with different neurotoxicity.I will further discuss how different fibril structures determine their distinct pathology under disease conditions.