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阿尔茨海默病的动物和细胞模型:进展、前景和未来方法。

Animal and Cellular Models of Alzheimer's Disease: Progress, Promise, and Future Approaches.

机构信息

Departamento Biologia Celular, Genetica y Fisiologia, Instituto de Investigacion Biomedica de Malaga-IBIMA, Facultad de Ciencias, Universidad de Malaga, Malaga, Spain.

Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.

出版信息

Neuroscientist. 2022 Dec;28(6):572-593. doi: 10.1177/10738584211001753. Epub 2021 Mar 26.

Abstract

Alzheimer's disease (AD) is an incurable neurodegenerative disease affecting over 45 million people worldwide. Transgenic mouse models have made remarkable contributions toward clarifying the pathophysiological mechanisms behind the clinical manifestations of AD. However, the limited ability of these in vivo models to accurately replicate the biology of the human disease have precluded the translation of promising preclinical therapies to the clinic. In this review, we highlight several major pathogenic mechanisms of AD that were discovered using transgenic mouse models. Moreover, we discuss the shortcomings of current animal models and the need to develop reliable models for the sporadic form of the disease, which accounts for the majority of AD cases, as well as human cellular models to improve success in translating results into human treatments.

摘要

阿尔茨海默病(AD)是一种无法治愈的神经退行性疾病,影响着全球超过 4500 万人。转基因小鼠模型在阐明 AD 临床表现背后的病理生理机制方面做出了显著贡献。然而,这些体内模型复制人类疾病生物学的能力有限,使得有希望的临床前治疗方法无法转化到临床。在这篇综述中,我们强调了使用转基因小鼠模型发现的 AD 的几个主要发病机制。此外,我们还讨论了当前动物模型的缺点,以及开发可靠的散发性疾病模型的必要性,因为散发性疾病占 AD 病例的大多数,以及开发人类细胞模型以提高将研究结果转化为人类治疗方法的成功率的必要性。

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