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阿尔茨海默病的实验模型用于解析发病机制和治疗筛选(综述)。

Experimental models of Alzheimer's disease for deciphering the pathogenesis and therapeutic screening (Review).

机构信息

Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Dongdan, Dong Cheng, Beijing 100005, P.R. China.

出版信息

Int J Mol Med. 2016 Feb;37(2):271-83. doi: 10.3892/ijmm.2015.2428. Epub 2015 Dec 10.

Abstract

Despite decades of laboratory and clinical research, Alzheimer's disease (AD) is still the leading cause of dementia in adults and there are no curative therapies currently available for this disease. This may be due to the pathological features of AD, which include extensive extracellular amyloid plaques and intracellular neurofibrillary tangles, as well as subsequent neuronal and synaptic loss, which begin to appear several years prior to memory loss and the damge is already irreversible and extensive at the time of clinical diagnosis. The poor therapeutic effects of current treatments necessitate the introduction of experimental models able to replicate AD pathology, particularly in the pre-symptomatic stage, and then to explore preventive and therapeutic strategies. In response to this necessity, various experimental models reproducing human AD pathology have been developed, which are also useful tools for therapeutic screening. Although none of these models fully reproduce the key features of human AD, the experimental models do provide important insight into the pathological changes which occur in AD. This review summarizes the commonly used experimental models of AD and also discusses how the models may be used to decipher the pathogenesis underlying AD and to screen novel therapies for this disease.

摘要

尽管经过了几十年的实验室和临床研究,阿尔茨海默病(AD)仍然是成年人痴呆的主要原因,目前尚无针对这种疾病的治愈疗法。这可能是由于 AD 的病理特征所致,包括广泛的细胞外淀粉样斑块和细胞内神经原纤维缠结,以及随后的神经元和突触丢失,这些丢失在记忆丧失之前的几年就开始出现,而且在临床诊断时已经不可逆转且广泛存在。目前治疗方法的疗效不佳,需要引入能够复制 AD 病理的实验模型,特别是在无症状阶段,然后探索预防和治疗策略。为了满足这一需求,已经开发出了各种复制人类 AD 病理的实验模型,这些模型也是治疗筛选的有用工具。尽管这些模型都不能完全复制人类 AD 的关键特征,但它们确实为 AD 中发生的病理变化提供了重要的见解。本综述总结了常用于 AD 的实验模型,并讨论了这些模型如何用于解析 AD 的发病机制和筛选该疾病的新疗法。

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