Aggregates from mutant and wild‐type α‐synuclein proteins and NAC peptide induce apoptotic cell death in human neuroblastoma cells by formation of β‐sheet and amyloid‐like filaments

FEBS Letters

El-Agnaf, Omar M.A¹  Pessi, Antonello⁴  Curran, Martin D⁵  Ingenito, Raffaele⁴  Bianchi, Elisabetta⁴  Middleton, Derek¹  Wallace, Andrew¹  Jakes, Ross²  Neill, David³ 

[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;Centre for the Health of the Elderly, Newcastle General Hospital, Westgate Road, Newcastle upon Tyne NE4 6BE, UK;Istituto di Ricerche di Biologia Molecolare (IRBM) P. Angeletti, Via Pontina Km 30.600, 00040 Pomezia (RM), Italy;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;    Toxicity;    Amyloid;    Neurodegenerative disease;    AD;    Alzheimer's disease;    Aβ;    β-amyloid protein;    ALS;    amyotrophic lateral sclerosis;    DLB;    dementia with Lewy bodies;    GCI;    glial cytoplasmic inclusion;    HD;    Huntington's disease;    LB;    Lewy body;    LN;    Lewy neurite;    MSA;    multiple system atrophy;    NAC;    non-Aβ component of AD amyloid;    PD;    Parkinson's disease;   

DOI  :  10.1016/S0014-5793(98)01418-5

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 and a fragment of it, called NAC, have 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 have shown that human wild-type α-syn, mutant α-syn(Ala30Pro) and mutant α-syn(Ala53Thr) proteins can self-aggregate and form amyloid-like filaments. Here we report that aggregates of NAC and α-syn proteins induced apoptotic cell death in human neuroblastoma SH-SY5Y cells. These findings indicate that accumulation of α-syn and its degradation products may play a major role in the development of the pathogenesis of these neurodegenerative diseases.

【 授权许可】

Unknown