M.-V. Guillot-Sestier and F. Checler Pages 304 - 315 ( 12 )
During the last thirty years, part of the scientific community focused on the mechanisms by which a naturally occurring protein called cellular prion (PrPc) converts into a protease-resistant isoform (PrPsc) responsible for fatal Transmissible Spongiform Encephalopathies (TSE). Concomitantly, the physiology of PrPc has also been studied. PrPc undergoes proteolytic attacks leading to both membrane-attached and secreted fragments, the nature of which differs in normal and TSE-affected human brains. Does proteolysis of PrPc correspond to an inactivating mechanism impairing the biological function of the protein, or alternatively, does it represent a maturation process allowing the produced fragments to trigger their own physiological function? Here we review the mechanisms involved in the production of PrPc catabolites and we focus on the function of PrPc and its derived fragments in the cell death/ survival regulation in the nervous system.
ADAM, α-secretase-derived fragments, apoptosis, βAPP, cellular Prion protein, neuroprotection, p53, PRNP gene, infectious agent, Creutzfeld-Jacob Disease, synthetic peptide, proteolysis, neurodegeneration, brain pathologies, amyloid plaques
Institut de Pharmacologie Moleculaire et Cellulaire and Institut de NeuroMedecine Moleculaire, Equipe labellisee Fondation pour laRecherche Medicale, 660 route des Lucioles, Sophia-Antipolis, 06560, Valbonne, France.