3-페닐-1-이소퀴놀린아민이 신경세포에서 베타 아밀로이드 전구단백질의 대사에 미치는 영향

Effects of 3-Phenyl-1-isoquinolinamine 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. Recently, we investigated that a quinoline compound from natural product reduced the secretion of Aβ from the neuroblastoma N2a cells (NL/N cell line) overexpressing APPswe. In this study, 3-phenyl-1-isoquinolinamine, a synthetic isoquinoline compound was analyzed to determine its effects on the metabolism of APP. It inhibited the secretion of Aβ peptides from the N2a NL/N cell line. Beta-site APP cleaving enzyme (BACE) fluorescence resonance energy transfer (FRET) assay revealed that it inhibited BACE activity in a dose dependent manner. Immunoblotting study showed that it inhibited APP stabilization and expression and it slightly increased the stablization and the expression of γ-secreatase component from the N2a NL/N cell line. We suggest that 3-phenyl-1-isoquinolinamine inhibits APP metabolism and Aβ generation by the means of BACE inhibitory mechanism. This is the first report that 3-phenyl-1-isoquinolinamine inhibits the secretion of Aβ peptides from neuroblastoma cells.