The broad-spectrum deubiquitinating enzyme inhibitor PR-619 protects retinal ganglion cell and augments parkin-mediated mitophagy in experimental glaucoma.

ABSTRACT: Glaucoma is a leading cause of irreversible visual impairment worldwide, characterized by the progressive death of retinal ganglion cells (RGCs). Deubiquitinating enzyme (DUB) inhibitors have shown promise as pharmacological interventions for neurodegenerative disorders. Our study focuses on the pan-DUB inhibitor PR-619 and its potential neuroprotective effects on RGCs through modulation of parkin-mediated mitophagy in experimental glaucoma models. The results show that impaired mitophagy exists in RGCs of our experimental glaucomatous model. In vivo, PR-619 increased RGCs survival in glaucomatous rats. In vitro, it protected RGCs against excitotoxicity and reduced ubiquitin-specific protease (USP) 15 expression. Additionally, PR-619 upregulated parkin expression, increased LC3-II/LC3-I ra

SUBMITTER: Hu X 

PROVIDER: S-EPMC11491476 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature