Neurotoxicity of acetylcholinesterase amyloid β‐peptide aggregates is dependent on the type of Aβ peptide and the AChE concentration present in the complexes

FEBS Letters

Muñoz, Francisco J.¹  Inestrosa, Nibaldo C.¹ 

[1] Departamento de Biologı́a Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, P.O. Box 114-D, Santiago, Chile

关键词: Alzheimer's disease;    Amyloid β1–40-peptide;    Amyloid β1–42-peptide;    Acetylcholinesterase;    Neurotoxicity;    PC12 cell;    AChE;    acetylcholinesterase;    Aβ;    amyloid β-peptide;    AD;    Alzheimer's disease;    MTT;    3-(4;    5-dimethylthiazol-2-yl)-2;    5-diphenyltetrazolium bromide;    CR;    Congo red;    Th-t;    thioflavine-t;    PBS;    phosphate buffered saline;    DMSO;    dimethyl sulfoxide;    PAGE;    polyacrylamide gel electrophoresis;    SDS;    sodium dodecyl sulfate;   

DOI  :  10.1016/S0014-5793(99)00468-8

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Alzheimer's disease (AD) is a neurodegenerative disorder whose hallmark is the presence of senile plaques and neurofibrillary tangles. Senile plaques are mainly composed of amyloid β-peptide (Aβ) fibrils and several proteins including acetylcholinesterase (AChE). AChE has been previously shown to stimulate the aggregation of Aβ_1–40 into amyloid fibrils. In the present work, the neurotoxicity of different amyloid aggregates formed in the absence or presence of AChE was evaluated in rat pheochromocytoma PC12 cells. Stable AChE-Aβ complexes were found to be more toxic than those formed without the enzyme, for Aβ_1–40 and Aβ_1–42, but not for amyloid fibrils formed with Aβ_Val18→Ala, a synthetic variant of the Aβ_1–40 peptide. Of all the AChE-Aβ complexes tested the one containing the Aβ_1–40 peptide was the most toxic. When increasing concentrations of AChE were used to aggregate the Aβ_1–40 peptide, the neurotoxicity of the complexes increased as a function of the amount of enzyme bound to each complex. Our results show that AChE-Aβ_1–40 aggregates are more toxic than those of AChE-Aβ_1–42 and that the neurotoxicity depends on the amount of AChE bound to the complexes, suggesting that AChE may play a key role in the neurodegeneration observed in Alzheimer brain.

【 授权许可】

Unknown