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靶向线粒体的天然产物:治疗与年龄相关的神经退行性疾病的新兴疗法。

Natural products targeting mitochondria: emerging therapeutics for age-associated neurological disorders.

机构信息

Cellular Neurobiology Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, United States; The Paul F. Glenn Center for Biology of Aging Research, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, United States.

Cellular Neurobiology Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, United States.

出版信息

Pharmacol Ther. 2021 May;221:107749. doi: 10.1016/j.pharmthera.2020.107749. Epub 2020 Nov 20.

Abstract

Mitochondria are the primary source of energy production in the brain thereby supporting most of its activity. However, mitochondria become inefficient and dysfunctional with age and to a greater extent in neurological disorders. Thus, mitochondria represent an emerging drug target for many age-associated neurological disorders. This review summarizes recent advances (covering from 2010 to May 2020) in the use of natural products from plant, animal, and microbial sources as potential neuroprotective agents to restore mitochondrial function. Natural products from diverse classes of chemical structures are discussed and organized according to their mechanism of action on mitochondria in terms of modulation of biogenesis, dynamics, bioenergetics, calcium homeostasis, and membrane potential, as well as inhibition of the oxytosis/ferroptosis pathway. This analysis emphasizes the significant value of natural products for mitochondrial pharmacology as well as the opportunities and challenges for the discovery and development of future neurotherapeutics.

摘要

线粒体是大脑能量产生的主要来源,从而支持其大部分活动。然而,线粒体随着年龄的增长而变得低效和功能失调,在神经疾病中更为严重。因此,线粒体成为许多与年龄相关的神经退行性疾病的新兴药物靶点。本综述总结了近年来(涵盖 2010 年至 2020 年 5 月)利用植物、动物和微生物来源的天然产物作为潜在神经保护剂来恢复线粒体功能的最新进展。讨论了具有不同化学结构类别的天然产物,并根据它们对线粒体的作用机制进行了组织,这些机制涉及生物发生、动力学、生物能学、钙稳态和膜电位的调节,以及对氧化/铁死亡途径的抑制。这种分析强调了天然产物在线粒体药理学方面的重要价值,以及发现和开发未来神经治疗药物的机遇和挑战。

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