Neuroprotective effect of naturally occurring RXR agonists isolated from Sophora tonkinensis Gagnep. on amyloid-β-induced cytotoxicity in PC12 cells.
作者： Takao Hirai , Makoto Inoue , Wei Wang , Ken-ichi Nakashima
DOI: 10.1007/S11418-019-01305-8
关键词:
摘要: Neuronal cell death induced by amyloid-β (Aβ) oligomers is implicated in neuronal degeneration and a leading cause of Alzheimer's disease (AD). Therefore, to identify effective therapeutic agents for AD, we investigated the neuroprotective effects two naturally occurring retinoid X receptor (RXR) agonists (SPF1 SPF2), isolated from root Sophora tonkinensis Gagnep., on Aβ25-35-induced cytotoxicity against nerve growth factor-differentiated rat pheochromocytoma (PC12) cells. Pretreatment with SPFs significantly prevented apoptosis PC12 cells, similarly synthetic RXR agonist bexarotene. These were blocked antagonist PA452. When studied presence liver (LXR) T0901317, protective enhanced, suggesting that RXR/LXR heterodimers may play key role SPFs. T0901317 ATP-binding cassette transporter 1 (ABCA1) protein expression cells when administered alone or combination. Intriguingly, functional inhibitor ABCA1 cyclosporine A negated T0901317. Taken together, these results demonstrate SPF1 SPF2 protect neurotoxicity an RXR-dependent manner their are markedly enhanced LXR part related function. suggest novel approach treatment prevention AD.
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