08-23-2021-0851 - Cellular prion protein transduces neuroprotective signals

EMBO J. 2002 Jul 1; 21(13): 3317–3326. 

doi: 10.1093/emboj/cdf324

PMCID: PMC125390

PMID: 12093733

Cellular prion protein transduces neuroprotective signals

Luciana B. Chiarini, Adriana R.O. Freitas,1,2 Silvio M. Zanata,1,2 Ricardo R. Brentani,1 Vilma R. Martins,1,3 and Rafael Linden4

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Abstract

To test for a role for the cellular prion protein (PrPc) in cell death, we used a PrPc-binding peptide. Retinal explants from neonatal rats or mice were kept in vitro for 24 h, and anisomycin (ANI) was used to induce apoptosis. The peptide activated both cAMP/protein kinase A (PKA) and Erk pathways, and partially prevented cell death induced by ANI in explants from wild-type rodents, but not from PrPc-null mice. Neuroprotection was abolished by treatment with phosphatidylinositol-specific phospholipase C, with human peptide 106–126, with certain antibodies to PrPc or with a PKA inhibitor, but not with a MEK/Erk inhibitor. In contrast, antibodies to PrPc that increased cAMP also induced neuroprotection. Thus, engagement of PrPc transduces neuroprotective signals through a cAMP/PKA-dependent pathway. PrPcmay function as a trophic receptor, the activation of which leads to a neuroprotective state.

Keywords: apoptosis/cell death/neuroprotection/prion/signal transduction

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC125390/

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