ArticleMolecules (Basel, Switzerland)2022
A Small Natural Molecule S3 Protects Retinal Ganglion Cells and Promotes Parkin-Mediated Mitophagy against Excitotoxicity.
Article in Molecules (Basel, Switzerland), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 16 citations in OpenAlex.
- Stage- and compartment-specific remodeling of autophagy and selective mitophagy in glaucoma: from aqueous outflow dysfunction to retinal ganglion cell neurodegeneration.Frontiers in cell and developmental biology · 2026Review
- Fucoxanthin protects retinal ganglion cells and regulates Parkin-mediated mitophagy in experimental glaucoma.BMJ open ophthalmology · 2025Article
- SHMT2 overexpression improves glaucoma by enhancing mitophagy in retinal ganglion cells through promoting the phospho of PINK1.Diagnostic pathology · 2025Article
- Electroacupuncture alleviates damage to myopic RGCs probably through lncRNA-XR_002789763.1-mediated mitophagy.Chinese medicine · 2025Article
- The Role of Autophagy in Excitotoxicity, Synaptic Mitochondrial Stress and Neurodegeneration.Autophagy reports · 2025Article
- Role of Tau Protein Hyperphosphorylation in Diabetic Retinal Neurodegeneration.Journal of ophthalmology · 2025Review
- Spotlight on USP30: structure, function, disease and target inhibition.Frontiers in pharmacology · 2025Review
- Mitochondria in Retinal Ganglion Cells: Unraveling the Metabolic Nexus and Oxidative Stress.International journal of molecular sciences · 2024Review
- Review
- Unveiling the potential of mitochondrial dynamics as a therapeutic strategy for acute kidney injury.Frontiers in cell and developmental biology · 2023Review
- Role of mitophagy in ocular neurodegeneration.Frontiers in neuroscience · 2023Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glutamate excitotoxicity may contribute to retinal ganglion cell (RGC) degeneration in glaucoma and other optic neuropathies, leading to irreversible blindness. Growing evidence has linked impaired mitochondrial quality control with RGCs degeneration, while parkin, an E3 ubiquitin ligase, has proved to be protective and promotes mitophagy in RGCs against excitotoxicity. The purpose of this study was to explore whether a small molecule S3 could modulate parkin-mediated mitophagy and has therapeutic potential for RGCs. The results showed that as an inhibitor of deubiquitinase USP30, S3 protected cultured RGCs and improved mitochondrial health against NMDA-induced excitotoxicity. Administration of S3 promoted the parkin expression and its downstream mitophagy-related proteins in RGCs. An upregulated ubiquitination level of Mfn2 and protein level of OPA1 were also observed in S3-treated RGCs, while parkin knockdown resulted in a major loss of the protective effect of S3 on RGCs under excitotoxicity. These findings demonstrated that S3 promoted RGC survival mainly through enhancing parkin-mediated mitophagy against excitotoxicity. The neuroprotective value of S3 in glaucoma and other optic neuropathies deserves further investigation.
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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.