The search for anti-oxytotic/ferroptotic compounds in the plant world.

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Oxytosis/ferroptosis is a form of non-apoptotic regulated cell death characterized by glutathione depletion and dysregulated production of mitochondrial reactive oxygen species 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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Authors: David Soriano-Castell, Zhibin Liang, Pamela Maher, Antonio Currais