A novel small molecule chaperone of rod opsin and its potential therapy for retinal degeneration.

ABSTRACT: Rhodopsin homeostasis is tightly coupled to rod photoreceptor cell survival and vision. Mutations resulting in the misfolding of rhodopsin can lead to autosomal dominant retinitis pigmentosa (adRP), a progressive retinal degeneration that currently is untreatable. Using a cell-based high-throughput screen (HTS) to identify small molecules that can stabilize the P23H-opsin mutant, which causes most cases of adRP, we identified a novel pharmacological chaperone of rod photoreceptor opsin, YC-001. As a non-retinoid molecule, YC-001 demonstrates micromolar potency and efficacy greater than 9-cis-retinal with lower cytotoxicity. YC-001 binds to bovine rod opsin with an EC₅₀ similar to 9-cis-retinal. The chaperone activity of YC-001 is evidenced by its ability to rescue the transport

SUBMITTER: Chen Y 

PROVIDER: S-EPMC5958115 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature