Targeting Mitophagy in Neurodegenerative Diseases: A Promising Therapeutic Avenue
Mitochondrial dysfunction is a central feature of several neurodegenerative diseases, including Parkinson’s disease, amyotrophic lateral sclerosis (ALS), Alzheimer’s disease, and Huntington’s disease. A groundbreaking study published in Nature Reviews Drug Discovery by Odetta Antico, Paul W. Thompson, Nicholas T. Hertz, Miratul M. K. Muqit, and Laura E. Parton highlights the potential of targeting mitophagy — the cellular process that eliminates damaged mitochondria — as a therapeutic strategy for these debilitating conditions.
Mutations in genes related to mitophagy deficits are often linked to familial forms of Parkinson’s disease and ALS. Enhancing the mitophagy pathway could address this underlying pathogenic mechanism, providing neuroprotection and disease-modifying effects—an urgent unmet need in neurodegenerative disease management.
Excitingly, small molecules aimed at enhancing mitophagy, such as USP30 inhibitors and PINK1 activators, are now entering phase I clinical trials. This marks a pivotal moment in translating preclinical evidence into potential treatments that could revolutionize care for patients affected by these devastating diseases.
Figure Description: Selective and non-selective mitophagy activators.
Read the full article: Nature Reviews Drug Discovery (2025).
