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Reverse electron transport (RET) at mitochondrial complex I generates reactive oxygen species (ROS) and reduces NAD+/NADH ratio. Inhibition of RET genetically or pharmacologically extends animal lifespan and ameliorates Alzheimer's disease©\related phenotypes.
CPT acts as an RET inhibitor by binding to complex I (C©\I) 30 kD subunit (C©\I30 or NDUFS3) and altering its interaction with other proteins in the soluble matrix arm of C©\I involved in electron transfer.
CPT was obtained from Cerepeut Inc. under a Materials Transfer Agreement between Cerepeut Inc. and Stanford University. The compound was synthesized for Cerepeut Inc. by the Chemistry Branch of Medicilon.
Reference:
Suman Rimal, et al. Reverse electron transfer is activated during aging and contributes to aging and age-related disease. EMBO Rep. 2023 Apr 5;24(4):e55548. doi: 10.15252/embr.202255548.