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Updated: Jun 2, 2025
07:56
Visualizing Mitophagy with Fluorescent Dyes for Mitochondria and Lysosome
Published on: November 30, 2022
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Targeting mitophagy in neurodegenerative diseases
Odetta Antico1,2, Paul W Thompson3, Nicholas T Hertz4
1MRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee, UK.
Nature Reviews. Drug Discovery
|January 14, 2025
Summary
Enhancing mitophagy, a cellular cleaning process, shows promise for treating neurodegenerative diseases like Parkinson's and Alzheimer's. Therapies targeting mitophagy deficits are now advancing to clinical trials.
Area of Science:
- Neuroscience
- Cell Biology
- Genetics
Background:
- Mitochondrial dysfunction is a key feature in neurodegenerative diseases such as Parkinson disease (PD), amyotrophic lateral sclerosis (ALS), Alzheimer disease (AD), and Huntington disease (HD).
- Genetic mutations linked to familial PD and ALS often impair mitophagy, a crucial cellular process for removing damaged mitochondria.
Purpose of the Study:
- To explore the therapeutic potential of enhancing the mitophagy pathway for neurodegenerative diseases.
- To highlight the unmet need for neuroprotection and disease modification in these conditions.
Main Methods:
- Review of genetic, molecular, and preclinical evidence supporting mitophagy enhancement.
- Identification of small-molecule mitophagy enhancers, including USP30 inhibitors and PINK1 activators.
Main Results:
- Strong evidence supports targeting mitophagy as a therapeutic strategy for neurodegenerative diseases.
- Small-molecule approaches for selective mitophagy enhancement are progressing.
Conclusions:
- Enhancing mitophagy offers a novel therapeutic avenue for neurodegenerative diseases by addressing underlying pathogenic mechanisms.
- USP30 inhibitors and PINK1 activators are entering Phase I clinical trials, representing a significant step forward.
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