Back to Search
Start Over
A Small Natural Molecule S3 Protects Retinal Ganglion Cells and Promotes Parkin-Mediated Mitophagy against Excitotoxicity.
- Source :
-
Molecules (Basel, Switzerland) [Molecules] 2022 Aug 04; Vol. 27 (15). Date of Electronic Publication: 2022 Aug 04. - Publication Year :
- 2022
-
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.
- Subjects :
- Glaucoma drug therapy
Glaucoma metabolism
Glutamic Acid metabolism
Humans
Mitochondrial Proteins antagonists & inhibitors
Mitochondrial Proteins metabolism
Neurotoxins metabolism
Optic Nerve Diseases drug therapy
Optic Nerve Diseases metabolism
Thiolester Hydrolases antagonists & inhibitors
Thiolester Hydrolases metabolism
Mitophagy drug effects
Mitophagy physiology
Neuroprotective Agents pharmacology
Neuroprotective Agents therapeutic use
Retinal Ganglion Cells drug effects
Retinal Ganglion Cells metabolism
Ubiquitin-Protein Ligases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1420-3049
- Volume :
- 27
- Issue :
- 15
- Database :
- MEDLINE
- Journal :
- Molecules (Basel, Switzerland)
- Publication Type :
- Academic Journal
- Accession number :
- 35956907
- Full Text :
- https://doi.org/10.3390/molecules27154957