A novel ER stress regulator ARL6IP5 induces reticulophagy to ameliorate the prion burden.

ABSTRACT: Prion disease is a fatal and infectious neurodegenerative disorder caused by the trans-conformation conversion of PRNP/PrP^C to PRNP/PrP^Sc. Accumulated PRNP/PrP^Sc-induced ER stress causes chronic unfolded protein response (UPR) activation, which is one of the fundamental steps in prion disease progression. However, the role of various ER-resident proteins in prion-induced ER stress is elusive. This study demonstrated that ARL6IP5 is compensatory upregulated in response to chronically activated UPR in the cellular prion disease model (RML-ScN2a). Furthermore, overexpression of ARL6IP5 overcomes ER stress by lowering the expression of chronically activated UPR pathway proteins. We discovered that ARL6IP5 induces reticulophagy to reduce the PRNP/PrP^Sc

SUBMITTER: Kamble K 

PROVIDER: S-EPMC11849938 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature