Hasan Md Fayad, Trushina Eugenia
Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA.
Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55905, USA.
Brain Sci. 2022 Apr 26;12(5):552. doi: 10.3390/brainsci12050552.
Alzheimer's disease (AD) is an incurable neurodegenerative disorder and the leading cause of death among older individuals. Available treatment strategies only temporarily mitigate symptoms without modifying disease progression. Recent studies revealed the multifaceted neurobiology of AD and shifted the target of drug development. Established animal models of AD are mostly tailored to yield a subset of disease phenotypes, which do not recapitulate the complexity of sporadic late-onset AD, the most common form of the disease. The use of human induced pluripotent stem cells (HiPSCs) offers unique opportunities to fill these gaps. Emerging technology allows the development of disease models that recapitulate a brain-like microenvironment using patient-derived cells. These models retain the individual's unraveled genetic background, yielding clinically relevant disease phenotypes and enabling cost-effective, high-throughput studies for drug discovery. Here, we review the development of various HiPSC-based models to study AD mechanisms and their application in drug discovery.
阿尔茨海默病（AD）是一种无法治愈的神经退行性疾病，也是老年人死亡的主要原因。现有的治疗策略只能暂时缓解症状，而无法改变疾病的进展。最近的研究揭示了AD多方面的神经生物学特性，并改变了药物研发的靶点。已建立的AD动物模型大多是为了产生一部分疾病表型而设计的，这些模型无法重现散发性晚发型AD（该疾病最常见的形式）的复杂性。人类诱导多能干细胞（HiPSC）的应用为填补这些空白提供了独特的机会。新兴技术使得利用患者来源的细胞开发能够重现类脑微环境的疾病模型成为可能。这些模型保留了个体未被揭示的遗传背景，产生与临床相关的疾病表型，并为药物发现提供了具有成本效益的高通量研究方法。在此，我们综述了各种基于HiPSC的模型在研究AD机制方面的进展及其在药物发现中的应用。
