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抗微生物和抗病毒药物在阿尔茨海默病中的应用。

The Use of Antimicrobial and Antiviral Drugs in Alzheimer's Disease.

机构信息

Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

出版信息

Int J Mol Sci. 2020 Jul 12;21(14):4920. doi: 10.3390/ijms21144920.

Abstract

The aggregation and accumulation of amyloid-β plaques and tau proteins in the brain have been central characteristics in the pathophysiology of Alzheimer's disease (AD), making them the focus of most of the research exploring potential therapeutics for this neurodegenerative disease. With success in interventions aimed at depleting amyloid-β peptides being limited at best, a greater understanding of the physiological role of amyloid-β peptides is needed. The development of amyloid-β plaques has been determined to occur 10-20 years prior to AD symptom manifestation, hence earlier interventions might be necessary to address presymptomatic AD. Furthermore, recent studies have suggested that amyloid-β peptides may play a role in innate immunity as an antimicrobial peptide. These findings, coupled with the evidence of pathogens such as viruses and bacteria in AD brains, suggests that the buildup of amyloid-β plaques could be a response to the presence of viruses and bacteria. This has led to the foundation of the antimicrobial hypothesis for AD. The present review will highlight the current understanding of amyloid-β, and the role of bacteria and viruses in AD, and will also explore the therapeutic potential of antimicrobial and antiviral drugs in Alzheimer's disease.

摘要

淀粉样β斑块和tau 蛋白在大脑中的聚集和积累是阿尔茨海默病(AD)病理生理学的核心特征,这使得它们成为大多数探索这种神经退行性疾病潜在治疗方法的研究的焦点。针对淀粉样β肽的干预措施取得的成功非常有限,因此需要更好地了解淀粉样β肽的生理作用。淀粉样β斑块的形成已被确定发生在 AD 症状出现前 10-20 年,因此可能需要更早的干预措施来解决前驱期 AD。此外,最近的研究表明,淀粉样β肽可能作为一种抗菌肽在先天免疫中发挥作用。这些发现,加上 AD 大脑中存在病毒和细菌等病原体的证据,表明淀粉样β斑块的堆积可能是对病毒和细菌存在的反应。这导致了 AD 的抗菌假说的建立。本文将重点介绍目前对淀粉样β的理解,以及细菌和病毒在 AD 中的作用,并探讨抗菌和抗病毒药物在阿尔茨海默病中的治疗潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fd0/7404195/bb5ed66d123d/ijms-21-04920-g001.jpg

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