EDEM Function in ERAD Protects against Chronic ER Proteinopathy and Age-Related Physiological Decline in Drosophila.

ABSTRACT: The unfolded protein response (UPR), which protects cells against accumulation of misfolded proteins in the ER, is induced in several age-associated degenerative diseases. However, sustained UPR activation has negative effects on cellular functions and may worsen disease symptoms. It remains unknown whether and how UPR components can be utilized to counteract chronic ER proteinopathies. We found that promotion of ER-associated degradation (ERAD) through upregulation of ERAD-enhancing α-mannosidase-like proteins (EDEMs) protected against chronic ER proteinopathy without inducing toxicity in a Drosophila model. ERAD activity in the brain decreased with aging, and upregulation of EDEMs suppressed age-dependent behavioral decline and extended the lifespan without affecting the UPR gene express

SUBMITTER: Sekiya M 

PROVIDER: S-EPMC5559287 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature