Journal
BRITISH JOURNAL OF PHARMACOLOGY
Volume 178, Issue 18, Pages 3611-3626Publisher
WILEY
DOI: 10.1111/bph.15517
Keywords
dementia; drug discovery; lipid peroxidation; oxidative stress; plant secondary metabolites; phenotypic screening
Categories
Funding
- National Institutes of Health [R01AG069206]
- Shiley-Marcos Alzheimer's Disease Research Center at University of California San Diego
- Paul F. Glenn Center for Biology of Aging Research
- Shiley Foundation
- Salk Institute
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Oxytosis/ferroptosis is a form of non-apoptotic regulated cell death with significant physiological implications for developing new therapeutic approaches. Plants, due to their sessile nature, have evolved a rich array of chemical strategies to cope with challenging conditions. This review highlights the potential of plant-based research in developing new medicines and promoting sustainability.
Oxytosis/ferroptosis is a form of non-apoptotic regulated cell death characterized by glutathione (GSH) depletion and dysregulated production of mitochondrial ROS that results in lethal lipid peroxidation. As the significance of oxytosis/ferroptosis to age-associated human diseases is now beginning to be appreciated, the development of innovative approaches to identify novel therapeutics that target the oxytosis/ferroptosis pathway could not be more timely. Due to their sessile nature, plants are exposed to a variety of stresses that trigger physiological changes similar to those found in oxytosis/ferroptosis. As such, they have evolved a rich array of chemical strategies to deal with those challenging conditions. This review details a drug discovery approach for identifying potent inhibitors of oxytosis/ferroptosis from plants for the treatment of Alzheimer's disease and related dementias, thereby highlighting the tremendous potential of plant-based research for developing new medicines while simultaneously being a catalyst for sustainability.
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