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阿尔茨海默病的鼻内淀粉样蛋白模型——潜在机遇与挑战

Intranasal amyloid model of Alzheimer's disease - potential opportunities and challenges.

作者信息

Singh Rakesh Kumar

机构信息

Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Raebareli. Transit campus, Bijnour-sisendi road, Sarojini nagar, Lucknow, 226002, Uttar Pradesh, India.

出版信息

Pharmacol Rep. 2025 Apr;77(2):425-433. doi: 10.1007/s43440-024-00692-4. Epub 2025 Jan 8.

Abstract

Amyloid beta 1-42 (Aβ) peptide is one of the most studied disease-related amyloidogenic peptides implicated in the pathophysiology of Alzheimer's disease (AD). Despite significant scientific breakthroughs in the recent past, the existing non-transgenic animal models do not demonstrate accurate pathology of AD progression. This review has presented a concise mechanistic understanding of the intranasal amyloid-based animal model of AD, along with its advantages, challenges, and major limitations. Furthermore, discussions on how to combat these challenges to pave the road toward developing novel therapeutics for AD, have also been included. Preclinical exploration of repeated intranasal amyloid-beta exposure would certainly aid the translational development of a robust animal model of AD. This will also provide a better understanding of disease progression and pathology in the intranasal animal model.

摘要

淀粉样β蛋白1-42(Aβ)肽是研究最多的与疾病相关的淀粉样生成肽之一,与阿尔茨海默病(AD)的病理生理学有关。尽管最近取得了重大科学突破,但现有的非转基因动物模型并未准确显示AD进展的病理学特征。本综述简要阐述了基于鼻内注射淀粉样蛋白的AD动物模型的作用机制,以及其优势、挑战和主要局限性。此外,还讨论了如何应对这些挑战,为开发AD新型疗法铺平道路。对重复鼻内注射淀粉样β蛋白进行临床前探索,肯定有助于建立一个强大的AD动物模型并将其转化应用。这也将有助于更好地理解鼻内动物模型中的疾病进展和病理学特征。

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