Department of Neurosciences, Case Western Reserve University, Cleveland, OH 44106 and Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202.
Department of Neurosciences, Case Western Reserve University, Cleveland, OH 44106 and Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202
J Lipid Res. 2017 Oct;58(10):1937-1949. doi: 10.1194/jlr.R075556. Epub 2017 Mar 6.
Alzheimer's disease (AD) is characterized by an extensive accumulation of amyloid-β (Aβ) peptide, which triggers a set of deleterious processes, including synaptic dysfunction, inflammation, and neuronal injury, leading to neuronal loss and cognitive impairment. A large body of evidence supports that nuclear receptor (NR) activation could be a promising therapeutic approach for AD. NRs are ligand-activated transcription factors that regulate gene expression and have cell type-specific effects. In this review, we discuss the mechanisms that underlie the beneficial effects of NRs in AD. Moreover, we summarize studies reported in the last 10-15 years and their major outcomes arising from the pharmacological targeting of NRs in AD animal models. The dissection of the pathways regulated by NRs in the context of AD is of importance in identifying novel and effective therapeutic strategies.
阿尔茨海默病（AD）的特征是淀粉样β（Aβ）肽的广泛积累，这触发了一系列有害过程，包括突触功能障碍、炎症和神经元损伤，导致神经元丧失和认知障碍。大量证据支持核受体（NR）的激活可能是治疗 AD 的一种有前途的方法。NR 是配体激活的转录因子，可调节基因表达，并具有细胞类型特异性作用。在这篇综述中，我们讨论了 NR 在 AD 中的有益作用的机制。此外，我们总结了过去 10-15 年中报道的研究及其在 AD 动物模型中通过药理学靶向 NR 产生的主要结果。在 AD 背景下解析 NR 调节的途径对于确定新的有效治疗策略非常重要。
