Pharmacological Inhibition of the VCP/Proteasome Axis Rescues Photoreceptor Degeneration in RHO^P23H Rat Retinal Explants.

ABSTRACT: Rhodopsin (RHO) misfolding mutations are a common cause of the blinding disease autosomal dominant retinitis pigmentosa (adRP). The most prevalent mutation, RHO^P23H, results in its misfolding and retention in the endoplasmic reticulum (ER). Under homeostatic conditions, misfolded proteins are selectively identified, retained at the ER, and cleared via ER-associated degradation (ERAD). Overload of these degradation processes for a prolonged period leads to imbalanced proteostasis and may eventually result in cell death. ERAD of misfolded proteins, such as RHO^P23H, includes the subsequent steps of protein recognition, targeting for ERAD, retrotranslocation, and proteasomal degradation. In the present study, we investigated and compared pharmacological modu

SUBMITTER: Sen M 

PROVIDER: S-EPMC8534135 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature