Anti-LRP/LR specific antibody IgG1-iS18 and knock-down of LRP/LR by shRNAs rescue cells from Aβ 42 induced cytotoxicity

Abstract

Alzheimer's disease (AD) is characterized by neurofibrillary tangles, senile plaques and neuronal loss. Amyloid beta (Aβ) is proposed to elicit neuronal loss through cell surface receptors. As Aβ shares common binding partners with the 37â€...kDa/67â€...kDa laminin receptor (LRP/LR), we investigated whether these proteins interact and the pathological significance of this association. An LRP/LR-Î'β 42 interaction was assessed by immunofluorescence microscopy and pull down assays. The cell biological effects were investigated by 3-(4,5-Dimethylthaizol-2-yl)-2,5- diphenyltetrazolium bromide and Bromodeoxyuridine assays. LRP/LR and Î'β 42 co-localised on the cell surface and formed immobilized complexes suggesting an interaction. Antibody blockade by IgG1-iS18 and shRNA mediated down regulation of LRP/LR significantly enhanced cell viability and proliferation in cells co-treated with Î'β 42 when compared to cells incubated with Î'β 42 only. Results suggest that LRP/LR is implicated in Î'β 42 mediated cytotoxicity and that anti-LRP/LR specific antibodies and shRNAs may serve as potential therapeutic tools for AD.