AMYLOID PROTEIN PROCESSING AND POTENTIAL TARGET OF ALZHEIMER DISEASE

Abstract

Human stem cell models serve as the potential to provide platforms for phenotypic screens to recognize candidate treatments and associated cellular pathways involved in the pathogenesis of Alzheimer disease (AD). Amyloid precursor protein (APP) processing and their derivatives like amyloid-β (Aβ) peptides generation are crucial processes involved in Alzheimer’s disease (AD). Identification of modulators of APP processing was processed phenotypically to screen out a small-molecule in TS21 derived neurons. Avermectins identified as modulators in neural cells, can raise the relative production of non-toxic short Aβ peptides in human cortical neurons at the expense of potentially more toxic longer peptides. Further, it was demonstrated that this avermectins effect is not only just because of interaction with the core γ-secretase and it iscrucial for Aβ production.  Although this study reflects the avermectinscould be prime targets of GABAA or glycine receptors, and may be possible reasons which affect Aβ peptides processing.

Keywords: avermectin, amyloid, γ-secretase, neural cells, Alzheimer, pathogenesis