Protective role of cellular prion protein against TNFα-mediated inflammation through TACE α-secretase.

ABSTRACT: Although cellular prion protein PrP^C is well known for its implication in Transmissible Spongiform Encephalopathies, its functions remain elusive. Combining in vitro and in vivo approaches, we here show that PrP^C displays the intrinsic capacity to protect neuronal cells from a pro-inflammatory TNFα noxious insult. Mechanistically, PrP^C coupling to the NADPH oxidase-TACE α-secretase signaling pathway promotes TACE-mediated cleavage of transmembrane TNFα receptors (TNFRs) and the release of soluble TNFR, which limits the sensitivity of recipient cells to TNFα. We further show that PrP^C expression is necessary for TACE α-secretase to stay at the plasma membrane in an active state for TNFR shedding. Such PrP^C control of TACE localization d

SUBMITTER: Ezpeleta J 

PROVIDER: S-EPMC5550509 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature