AAIC 2021 | Increasing eIF2a phosphorylation to boost protein quality control in neurodegenerative disease

Anne Bertolotti, PhD, FMedSci, MRC Laboratory of Molecular Biology, Cambridge, UK, outlines the development of Raphin1, a selective inhibitor of R15B. Studies in experimental models of neurodegenerative diseases have shown that inhibition of the PP1 phosphatase regulatory subunit R15A with guanabenz and sephin1 impairs eIF2a recruitment and subsequent dephosphorylation. This activity was found to improve cell survival by protecting cells from protein misfolding stress. Related regulatory subunit R15B is constitutively expressed, making it a better target than the inducible R15A. This interview took place during the Alzheimer’s Association International Conference (AAIC) 2021.