Targeting mitophagy in neurodegenerative diseases

Output Details

Published January 14, 2025

Mitochondrial dysfunction is a hallmark of idiopathic neurodegenerative diseases, including Parkinson disease, amyotrophic lateral sclerosis, Alzheimer disease and Huntington disease. Familial forms of Parkinson disease and amyotrophic lateral sclerosis are often characterized by mutations in genes associated with mitophagy deficits. Therefore, enhancing the mitophagy pathway may represent a novel therapeutic approach to targeting an underlying pathogenic cause of neurodegenerative diseases, with the potential to deliver neuroprotection and disease modification, which is an important unmet need. Accumulating genetic, molecular and preclinical model-based evidence now supports targeting mitophagy in neurodegenerative diseases. Despite clinical development challenges, small-molecule-based approaches for selective mitophagy enhancement — namely, USP30 inhibitors and PINK1 activators — are entering phase I clinical trials for the first time.
Tags
  • Mitochondrial dysfunction
  • Mitophagy
  • Neurodegenerative disorders
  • PINK1
  • Review
  • Therapeutic development

Meet the Authors

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    Odetta Antico

    Key Personnel: Team Alessi

    MRC Protein Phosphorylation and Ubiquitylation Unit

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    Paul Thompson

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    Nicholas Hertz

  • Miratul Muqit

    Co-PI (Core Leadership): Team Alessi

    University of Dundee

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    Laura Parton