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阿尔茨海默病中β淀粉样蛋白和tau蛋白的新兴药物靶点:一项系统综述

Emerging drug targets for Aβ and tau in Alzheimer's disease: a systematic review.

作者信息

West Sophie, Bhugra Praveen

机构信息

Sunderland Pharmacy School, Department of Pharmacy, Health and Wellbeing, The University of Sunderland, City Campus, Chester Road, Sunderland, SR1 3SD, United Kingdom.

出版信息

Br J Clin Pharmacol. 2015 Aug;80(2):221-34. doi: 10.1111/bcp.12621. Epub 2015 Jun 8.

Abstract

AIMS

Currently, treatment for Alzheimer's disease (AD) focuses on the cholinergic hypothesis and provides limited symptomatic effects. Research currently focuses on other factors that are thought to contribute to AD development such as tau proteins and Aβ deposits, and how modification of the associated pathology affects outcomes in patients. This systematic review summarizes and appraises the evidence for the emerging drugs affecting Aβ and tau pathology in AD.

METHODS

A comprehensive, systematic online database search was conducted using the databases ScienceDirect and PubMed to include original research articles. A systematic review was conducted following a minimum set of standards, as outlined by The PRISMA Group . Specific inclusion and exclusion criteria were followed and studies fitting the criteria were selected. No human trials were included in this review. In vitro and in vivo AD models were used to assess efficacy to ensure studied agents were emerging targets without large bodies of evidence.

RESULTS

The majority of studies showed statistically significant improvement (P < 0.05) of Aβ and/or tau pathology, or cognitive effects. Many studies conducted in AD animal models have shown a reduction in Aβ peptide burden and a reduction in tau phosphorylation post-intervention. This has the potential to reduce plaque formation and neuronal degeneration.

CONCLUSIONS

There are many emerging targets showing promising results in the effort to modify the pathological effects associated with AD. Many of the trials also provided evidence of the clinical effects of such drugs reducing pathological outcomes, which was often demonstrated as an improvement of cognition.

摘要

目的

目前,阿尔茨海默病(AD)的治疗聚焦于胆碱能假说,且仅能提供有限的对症治疗效果。当前的研究集中在其他被认为与AD发病相关的因素,如tau蛋白和Aβ沉积,以及相关病理改变的调整如何影响患者的预后。本系统评价总结并评估了影响AD中Aβ和tau病理改变的新兴药物的证据。

方法

使用ScienceDirect和PubMed数据库进行全面、系统的在线数据库检索,以纳入原始研究文章。按照PRISMA小组概述的最低标准进行系统评价。遵循特定的纳入和排除标准,选择符合标准的研究。本评价未纳入人体试验。使用体外和体内AD模型评估疗效,以确保所研究的药物是新兴靶点,且缺乏大量证据。

结果

大多数研究显示,Aβ和/或tau病理改变或认知效应有统计学意义的改善(P < 0.05)。在AD动物模型中进行的许多研究表明,干预后Aβ肽负荷降低,tau磷酸化减少。这有可能减少斑块形成和神经元变性。

结论

在努力改变与AD相关的病理效应方面,有许多新兴靶点显示出了有前景的结果。许多试验还提供了此类药物降低病理结局的临床效果的证据,这通常表现为认知功能的改善。

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