Department of Bioinnovation Center, Buddhist Tzu Chi Medical foundation, Hualien 97002, Taiwan.
Department of Life Science, National Dong Hwa University, Hualien 97401, Taiwan.
Int J Mol Sci. 2020 Feb 16;21(4):1327. doi: 10.3390/ijms21041327.
Alzheimer's disease (AD) is characterized by extracellular amyloid plaques composed of the β-amyloid peptides and intracellular neurofibrillary tangles and associates with progressive declines in memory and cognition. Several genes play important roles and regulate enzymes that produce a pathological accumulation of β-amyloid in the brain, such as gamma secretase (γ-secretase). Induced pluripotent stem cells from patients with Alzheimer's disease with different underlying genetic mechanisms may help model different phenotypes of Alzheimer's disease and facilitate personalized drug screening platforms for the identification of small molecules. We also discuss recent developments by γ-secretase inhibitors and modulators in the treatment of AD. In addition, small-molecule drugs isolated from Chinese herbal medicines have been shown effective in treating Alzheimer's disease. We propose a mechanism of small-molecule drugs in treating Alzheimer's disease. Combining therapy with different small-molecule drugs may increase the chance of symptomatic treatment. A customized strategy tailored to individuals and in combination with therapy may be a more suitable treatment option for Alzheimer's disease in the future.
阿尔茨海默病(AD)的特征是细胞外由β-淀粉样肽组成的淀粉样斑块和细胞内的神经原纤维缠结,并伴有记忆和认知能力的逐渐下降。有几个基因发挥了重要作用,并调节产生大脑中病理性β-淀粉样物质积累的酶,如γ-分泌酶(γ-secretase)。来自具有不同潜在遗传机制的阿尔茨海默病患者的诱导多能干细胞可能有助于模拟不同的阿尔茨海默病表型,并促进个性化药物筛选平台,以识别小分子。我们还讨论了γ-分泌酶抑制剂和调节剂在 AD 治疗中的最新进展。此外,从中药中分离出的小分子药物已被证明对治疗阿尔茨海默病有效。我们提出了小分子药物治疗阿尔茨海默病的一种机制。联合使用不同的小分子药物治疗可能会增加症状治疗的机会。针对个体的定制化策略与联合治疗相结合,可能是未来阿尔茨海默病更合适的治疗选择。