4.7 Review

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

Journal

PHARMACOLOGY & THERAPEUTICS
Volume 221, Issue -, Pages -

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pharmthera.2020.107749

Keywords

Natural products; mitochondrial dysfunction; oxytosis; ferroptosis; aging; neurological disorders; neuropharmacology; drug discovery

Funding

  1. Paul F. Glenn Center for Biology of Aging Research at the Salk Institute Fellowship Award
  2. Innovation Award from the Salk Institute
  3. Shiley-Marcos Alzheimer's Disease Research Center at the University of California, San Diego
  4. Edward N. & Della Thome Memorial Foundation
  5. National Institutes of Health [R01AG046153, RF1AG054714, R21AG064287, R41AI104034]

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Mitochondria, as the primary source of energy production in the brain, become inefficient and dysfunctional with age and in neurological disorders. Natural products are utilized as potential neuroprotective agents to restore mitochondrial function, highlighting both the value and challenges in the discovery and development of future neurotherapeutics.
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. (c) 2020 Elsevier Inc. All rights reserved.

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