Effects of the mutations Ala30 to Pro and Ala53 to Thr on the physical and morphological properties of α‐synuclein protein implicated in Parkinson's disease

FEBS Letters

El-Agnaf, Omar M.A¹  Curran, Martin D³  Wallace, Andrew¹  Jakes, Ross² 

[1] Centre for Peptide and Protein Engineering, School of Biology and Biochemistry, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK;Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK;Northern Ireland Histocompatibility and Immunogenetics Laboratory, Belfast City Hospital, Lisburn Road, Belfast BT9 7AB, UK

关键词: α-Synuclein;    Parkinson's disease;    Lewy body;    Self-aggregation;    Amyloid;    Neurodegenerative disease;    AD;    Alzheimer's disease;    Aβ;    β-amyloid protein;    DLB;    dementia with Lewy bodies;    HD;    Huntington's disease;    LB;    Lewy body;    LN;    Lewy neurite;    NAC;    non-Aβ component of AD amyloid;    PD;    Parkinson's disease;   

DOI  :  10.1016/S0014-5793(98)01419-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

α-Synuclein (α-syn) protein has been found in association with the pathological lesions of a number of neurodegenerative diseases. Recently, mutations in the α-syn gene have been reported in families susceptible to an inherited form of Parkinson's disease. We report here that human wild-type α-syn, PD-linked mutant α-syn(Ala30Pro) and mutant α-syn(Ala53Thr) proteins can self-aggregate and form amyloid-like filaments. The mutant α-syn forms more β-sheet and mature filaments than the wild-type protein. These findings suggest that accumulation of α-syn as insoluble deposits of amyloid may play a major role in the pathogenesis of these neurodegenerative diseases.

【 授权许可】

Unknown