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阿尔茨海默病中的淀粉样β假说:主要罪魁祸首和近期治疗策略。

Amyloid Beta Hypothesis in Alzheimer's Disease: Major Culprits and Recent Therapeutic Strategies.

机构信息

Laboratory for Structural Bioinformatics, Center for Biosystems Dynamics Research, RIKEN, 1-7-22 Suehiro, Tsurumi, Yokohama, Kanagawa 230-0045, Japan.

Department of Biotechnology and Microbiology, Thalassery Campus, Kannur University, Kerala Pin 670 661, India.

出版信息

Curr Drug Targets. 2020;21(2):148-166. doi: 10.2174/1389450120666190806153206.

Abstract

Alzheimer's disease (AD) is one of the most common forms of dementia and has been a global concern for several years. Due to the multi-factorial nature of the disease, AD has become irreversible, fatal and imposes a tremendous socio-economic burden. Even though experimental medicines suggested moderate benefits, AD still lacks an effective treatment strategy for the management of symptoms or cure. Among the various hypotheses that describe development and progression of AD, the amyloid hypothesis has been a long-term adherent to the AD due to the involvement of various forms of Amyloid beta (Aβ) peptides in the impairment of neuronal and cognitive functions. Hence, majority of the drug discovery approaches in the past have focused on the prevention of the accumulation of Aβ peptides. Currently, there are several agents in the phase III clinical trials that target Aβ or the various macromolecules triggering Aβ deposition. In this review, we present the state of the art knowledge on the functional aspects of the key players involved in the amyloid hypothesis. Furthermore, we also discuss anti-amyloid agents present in the Phase III clinical trials.

摘要

阿尔茨海默病(AD)是最常见的痴呆症形式之一,多年来一直是全球关注的焦点。由于该疾病的多因素性质,AD 已经变得不可逆转、致命,并造成了巨大的社会经济负担。尽管实验药物表明有适度的益处,但 AD 仍然缺乏有效的治疗策略来管理症状或治愈疾病。在描述 AD 发展和进展的各种假说中,淀粉样蛋白假说由于各种形式的淀粉样蛋白 β (Aβ) 肽参与损害神经元和认知功能而长期以来一直是 AD 的忠实支持者。因此,过去大多数药物发现方法都集中在预防 Aβ 肽的积累上。目前,有几种针对 Aβ 或触发 Aβ 沉积的各种大分子的药物正在进行 III 期临床试验。在这篇综述中,我们介绍了淀粉样蛋白假说涉及的关键分子的功能方面的最新知识。此外,我们还讨论了 III 期临床试验中存在的抗淀粉样蛋白药物。

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