Radicicol이 신경세포에서 베타 아밀로이드 전구단백질의 대사에 미치는 영향

Effects of Radicicol on the Metabolism of β-Amyloid Precursor Protein in Neuroblastoma Cells

Alzheimer’s disease (AD) is characterized pathologically by the presence of intracellular neurofibrillary tangles and deposition of β-amyloid (Aβ) peptides, which are generated by processing of amyloid precursor protein (APP). It is urgent to develop effective therapies for the treatment of AD, since our society rapidly accelerate aging. Aβ peptides have been believed to be neurotoxic and now are also considered to have effects on the mechanism of memory formation. In this study, effects of radicicol on the metabolism of APP were analyzed. Radicicol inhibited the secretion of Aβ from the Neuro2a cell line (APPswe cell) expressing APPswe. Beta-site APP cleaving enzyme (BACE) fluorescence resonance energy transfer (FRET) assay revealed that it inhibited BACE activity in a dose dependently manner. Immunoblotting study showed that it inhibited intracellular heat shock protein (HSP)90 and it increased the secretion of HSP90 from the APPswe cells. We suggest that radicicol inhibits APP metabolism and Aβ generation by the means of HSP90 inhibitory mechanism and partially BACE inhibitory mechanism. This is the first report that radicicol inhibits the secretion of Aβ peptides from neuroblastoma cells.