A Soluble PrP^C Derivative and Membrane-Anchored PrP^C in Extracellular Vesicles Attenuate Innate Immunity by Engaging the NMDA-R/LRP1 Receptor Complex.

ABSTRACT: Nonpathogenic cellular prion protein (PrP^C) demonstrates anti-inflammatory activity; however, the responsible mechanisms are incompletely defined. PrP^C exists as a GPI-anchored membrane protein in diverse cells; however, PrP^C may be released from cells by ADAM proteases or when packaged into extracellular vesicles (EVs). In this study, we show that a soluble derivative of PrP^C (S-PrP) counteracts inflammatory responses triggered by pattern recognition receptors in macrophages, including TLR2, TLR4, TLR7, TLR9, NOD1, and NOD2. S-PrP also significantly attenuates the toxicity of LPS in mice. The response of macrophages to S-PrP is mediated by a receptor assembly that includes the N-methyl-d-aspartate receptor (NMDA-R) and low-density lipopro

SUBMITTER: Mantuano E 

PROVIDER: S-EPMC8702456 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature