Cellular prion protein transduces neuroprotective signals

Author(s)

Chiarini, Luciana B. ; Freitas, Adriana R. O. ; Zanata, Silvio M. ; Brentani, Ricardo R. ; Martins, Vilma R. ^[5] ; Linden, Rafael

• Document type: Journal article
• Source: EMBO Journal; v. 21, n. 13, p. 3317-3326, July 2002.
• Field of knowledge: Biological Sciences - Biochemistry

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. PrPc may function as a trophic receptor, the activation of which leads to a neuroprotective state. (AU)

• FAPESP's process: 99/07124-8 - The role of celular prion protein in physiological and pathological processes
• Grantee: Vilma Regina Martins
• Support type: Research Projects - Thematic Grants