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β-内酰胺类抗生素抑制阿尔茨海默病的分子通路。

β-lactam antibiotics to tame down molecular pathways of Alzheimer's disease.

机构信息

Department of Pharmaceutical Sciences and Technology, Maharaja Ranjit Singh Punjab Technical University, Bathinda, 151001, Punjab, India.

Department of Pharmaceutical Sciences and Technology, Maharaja Ranjit Singh Punjab Technical University, Bathinda, 151001, Punjab, India.

出版信息

Eur J Pharmacol. 2021 Mar 15;895:173877. doi: 10.1016/j.ejphar.2021.173877. Epub 2021 Jan 14.

Abstract

Alzheimer's disease is a multifactorial disorder characterized by extracellular accumulation of amyloid-β (Aβ) and intracellular accumulations of neurofibrillary tangles. Numerous drug targets have been explored for therapeutic efficacy but failed to deliver successful treatments clinically. However, over the years our understanding of the disease pathophysiology increased significantly. Many of the novel targets which can cure or modify disease pathology are being explored preclinically as well as clinically. On contrarily, the drug discovery and development process is lengthy and the cost involved makes it difficult for faster translation of therapeutic outcomes. Therefore, repurposing existing drugs for a new therapeutic indication is considered a better approach and helps in the fast translation of therapeutic information. The existing drugs have well-proven records on their safety, pharmacokinetics, etc. In recent years, beta (β)-lactam antibiotics have been repurposed for the management of neurodegenerative pathologies. Here in the current review, we have explored β-lactam antibiotics, their target sites, molecular mechanisms, and their therapeutic potential in Alzheimer's disease.

摘要

阿尔茨海默病是一种多因素疾病,其特征是细胞外淀粉样蛋白-β(Aβ)的积累和细胞内神经原纤维缠结的积累。已经探索了许多药物靶点以提高治疗效果,但在临床上都未能成功。然而,多年来,我们对疾病发病机制的理解有了显著提高。许多可以治愈或改变疾病病理的新靶点正在进行临床前和临床研究。相反,药物发现和开发过程漫长,所涉及的成本使得治疗效果的更快转化变得困难。因此,将现有药物重新用于新的治疗适应症被认为是一种更好的方法,并有助于快速转化治疗信息。现有药物在安全性、药代动力学等方面已有良好的记录。近年来,β-内酰胺类抗生素已被重新用于治疗神经退行性病变。在本综述中,我们探讨了β-内酰胺类抗生素、它们的靶位、分子机制及其在阿尔茨海默病中的治疗潜力。

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