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关于临床前阿尔茨海默病模型的综合综述:评估其临床相关性

A Comprehensive Review on Preclinical Alzheimer's Disease Models: Evaluating their Clinical Relevance.

作者信息

Kushwaha Virendra, Sahu Kantrol Kumar

机构信息

Institute of Pharmaceutical Research, GLA University, Mathura, UP, 281406, India.

出版信息

Curr Pharm Biotechnol. 2025;26(2):186-207. doi: 10.2174/0113892010331845240802073645.

Abstract

Alzheimer's disease (AD) is a neurological disorder that increases with age and must be treated immediately by worldwide healthcare systems. Internal neurofibrillary tau tangles and extracellular amyloid accumulation have been widely recognized as the primary causes of Alzheimer's disease. These degenerative age-related ailments are expected to proliferate exponentially as life expectancy rises. Experimental models of AD are essential for acquiring a deep knowledge of its pathogenesis and determining the viability of novel therapy options. Although there isn't a model that encompasses all the characteristics of real AD, these models are nonetheless highly helpful for the research of various modifications associated with it, even though they are only partially indicative of the disease circumstances being studied. Better knowledge of the advantages and disadvantages of each of the different models, as well as the use of more than one model to evaluate potential medications, would increase the effectiveness of therapy translation from preclinical research to patients. We outline the pathogenic characteristics and limitations of the main experimental models of AD in this review, including transgenic mice, transgenic rats, primates and non-primate models along with cell culture models in humans. Additionally, it highlights the possible future of experimental modeling of AD and includes the co-morbid models.

摘要

阿尔茨海默病(AD)是一种随年龄增长而增加的神经疾病,全球医疗保健系统必须立即对其进行治疗。神经内神经原纤维缠结和细胞外淀粉样蛋白积累已被广泛认为是阿尔茨海默病的主要原因。随着预期寿命的增加,这些与年龄相关的退行性疾病预计将呈指数级增长。AD的实验模型对于深入了解其发病机制和确定新治疗方案的可行性至关重要。尽管没有一个模型能涵盖真实AD的所有特征,但这些模型对于研究与之相关的各种变化仍然非常有帮助,尽管它们只是部分地反映了所研究的疾病情况。更好地了解每种不同模型的优缺点,以及使用多种模型来评估潜在药物,将提高从临床前研究到患者的治疗转化效果。在本综述中,我们概述了AD主要实验模型的致病特征和局限性,包括转基因小鼠、转基因大鼠、灵长类和非灵长类模型以及人类细胞培养模型。此外,它还强调了AD实验建模的可能未来,并包括共病模型。

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