Laminin 1 attenuates β-amyloid peptide Aβ(1-40) neurotoxicity of cultured fetal rat cortical neurons

Abstract

A growing amount of evidence indicates the involvement of extracellular matrix components, especially laminins, in the development of Alzheimer's disease, although their role remains unclear. In this study, we clearly demonstrate that laminin 1 inhibits β-amyloid peptide (Aβ)-induced neuronal cell death by preventing the fibril formation and interaction of the Aβ peptide with cell membranes. The presence of laminin at a laminin/Aβ peptide molar ratio of 1:800 significantly inhibits the Aβ-induced apoptotic events, together with inhibition of amyloid fibril formation. The inhibitory effects of laminin 1 were time- and dose-dependent, whereas laminin 2 had less effect on Aβ neurotoxicity. A preincubation of laminin and Aβ was not required to observe the protective effect of laminin, suggesting a direct interaction between laminin 1 and Aβ. Moreover, laminin had no effect on the toxicity of the fibrillar Aβ peptide, suggesting an interaction of laminin with nonfibrillar species of the Aβ peptide, sequestering the peptide in a soluble form. These data extend our understanding of laminin-dependent binding of Aβ and highlight the possible modulation role of laminin regarding Aβ aggregation and neurotoxicity in vivo.