Medicine and Health

Pharmacological targeting of MCL-1 promotes mitophagy and improves disease pathologies in an Alzheimer's disease mouse model

X. Cen, Y. Chen, et al.

This groundbreaking study reveals the therapeutic potential of UMI-77, a drug that activates neuronal mitophagy, targeting MCL-1 as a receptor. Conducted by Xufeng Cen and colleagues, it shows promise for reversing Alzheimer’s disease symptoms through potent mitophagy activation. A game-changer in Alzheimer's treatment!

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Abstract

This study investigates the therapeutic potential of inducing neuronal mitophagy for Alzheimer's disease. A screen of FDA-approved drugs identified UMI-77, a BH3-mimetic targeting MCL-1, as a potent mitophagy activator at sub-lethal doses. Mechanistic studies revealed MCL-1 as a mitophagy receptor directly binding to LC3A. In vivo studies using an APP/PS1 mouse model demonstrated that UMI-77 effectively reversed molecular and behavioral disease phenotypes by inducing mitophagy. These findings highlight MCL-1 as a potential drug target for Alzheimer's disease treatment.

Publisher

Nature Communications

Published On

Nov 12, 2020

Authors

Xufeng Cen, Yanying Chen, Xiaoyan Xu, Ronghai Wu, Fusheng He, Qingwei Zhao, Qiming Sun, Cong Yi, Jie Wu, Ayaz Najafov, Hongguang Xia

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