Interactions of laminin with the amyloid ß peptide: Implications for Alzheimer's disease

Brazilian Journal of Medical and Biological Research

C. Morgan¹  N.c. Inestrosa¹ 

[1] ,Pontificia Universidad Católica de Chile Facultad de Ciencias Biológicas Departamento de Biología Celular y MolecularSantiago,Chile

关键词: extracellular matrix;    laminin;    amyloid ß peptide;    neuronal injury;    neurodegenerative disease;   

DOI  :  10.1590/S0100-879X2001000500006

来源: SciELO

【 摘 要 】

Extensive neuronal cell loss is observed in Alzheimer's disease. Laminin immunoreactivity colocalizes with senile plaques, the characteristic extracellular histopathological lesions of Alzheimer brain, which consist of the amyloid ß (Aß) peptide polymerized into amyloid fibrils. These lesions have neurotoxic effects and have been proposed to be a main cause of neurodegeneration. In order to understand the pathological significance of the interaction between laminin and amyloid, we investigated the effect of laminin on amyloid structure and toxicity. We found that laminin interacts with the Aß1-40 peptide, blocking fibril formation and even inducing depolymerization of preformed fibrils. Protofilaments known to be intermediate species of Aß fibril formation were also detected as intermediate species of laminin-induced Aß fibril depolymerization. Moreover, laminin-amyloid interactions inhibited the toxic effects on rat primary hippocampal neurons. As a whole, our results indicate a putative anti-amyloidogenic role of laminin which may be of biological and therapeutic interest for controlling amyloidosis, such as those observed in cerebral angiopathy and Alzheimer's disease.

【 授权许可】

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