ArticleThe Biochemical journal2021
Investigation of USP30 inhibition to enhance Parkin-mediated mitophagy: tools and approaches.
Article in The Biochemical journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 55 citations in OpenAlex.
- From synaptic development to degeneration: a narrative review of small molecule strategies targeting alpha-synuclein in Parkinson's disease.Metabolic brain disease · 2026Review
- Autophagy and mitophagy at the synapse and beyond: implications for learning, memory and neurological disorders.Autophagy · 2026Review
- Deubiquitinating enzymes at the crossroads of blood-brain barrier integrity and neurodegeneration: mechanistic insights, therapeutic targeting and future directions.Tissue barriers · 2026Review
- Activation of USP30 Disrupts Endothelial Cell Function and Aggravates Acute Lung Injury Through Regulating the S-Adenosylmethionine Cycle.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Insights into PINK1/Parkin function and dysfunction from Drosophila models.The Biochemical journal · 2025Review
- GNPAT/USP30 Stabilizes DRP1 Protein to Promote Mitochondrial Fission and Functional Damage in COPD Progression.The Kaohsiung journal of medical sciences · 2025Article
- USP30 inhibition augments mitophagy to prevent T cell exhaustion.Science advances · 2025Article
- YOD1 regulates oxidative damage of dopamine neurons in Parkinson's disease by deubiquitinating PKM2.Clinical and translational medicine · 2025Article
- Physiological roles and therapeutic implications of USP6.Cell death discovery · 2025Review
- Genetic mutations in kinases: a comprehensive review on marketed inhibitors and unexplored targets in Parkinson's disease.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025Review
- Targeting mitophagy in neurodegenerative diseases.Nature reviews. Drug discovery · 2025Review
- Structural Dynamics of the Ubiquitin Specific Protease USP30 in Complex with a Cyanopyrrolidine-Containing Covalent Inhibitor.Journal of proteome research · 2025Article
- Spotlight on USP30: structure, function, disease and target inhibition.Frontiers in pharmacology · 2025Review
- Molecular Symphony of Mitophagy: Ubiquitin-Specific Protease-30 as a Maestro for Precision Management of Neurodegenerative Diseases.CNS neuroscience & therapeutics · 2025Review
- Advances in autophagy for Parkinson's disease pathogenesis and treatment.Ageing and neurodegenerative diseases · 2025Article
- Structural and Functional Characterization of the Most Frequent Pathogenic PRKN Substitution p.R275W.Cells · 2024Article
- Exploring the Role of Ubiquitin-Proteasome System in the Pathogenesis of Parkinson's Disease.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Discovery of potent and selective activity-based probes (ABPs) for the deubiquitinating enzyme USP30.RSC chemical biology · 2024Article
- Variety in the USP deubiquitinase catalytic mechanism.Life science alliance · 2024Article
- USP30 inhibition induces mitophagy and reduces oxidative stress in parkin-deficient human neurons.Cell death & disease · 2024Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Mitochondrial dysfunction is implicated in Parkinson disease (PD). Mutations in Parkin, an E3 ubiquitin ligase, can cause juvenile-onset Parkinsonism, probably through impairment of mitophagy. Inhibition of the de-ubiquitinating enzyme USP30 may counter this effect to enhance mitophagy. Using different tools and cellular approaches, we wanted to independently confirm this claimed role for USP30. Pharmacological characterisation of additional tool compounds that selectively inhibit USP30 are reported. The consequence of USP30 inhibition by these compounds, siRNA knockdown and overexpression of dominant-negative USP30 on the mitophagy pathway in different disease-relevant cellular models was explored. Knockdown and inhibition of USP30 showed increased p-Ser65-ubiquitin levels and mitophagy in neuronal cell models. Furthermore, patient-derived fibroblasts carrying pathogenic mutations in Parkin showed reduced p-Ser65-ubiquitin levels compared with wild-type cells, levels that could be restored using either USP30 inhibitor or dominant-negative USP30 expression. Our data provide additional support for USP30 inhibition as a regulator of the mitophagy pathway.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.