title: Prion and TNFα: TAC(E)it agreement between the prion protein and cell signaling.
abstract: Prion diseases are rare and fatal neurodegenerative disorders that occur when the cellular prion protein (PrPC) is converted into a conformationally modified isoform that originates the novel infectious agent, called prion. Although much information is now available on the different routes of prion infection, both the mechanisms underlying prion neurotoxicity and the physiologic role of PrPC remain unclear. By use of a novel paradigm, we have shown in a recent paper that--following a myotoxin-induced degenerative challenge--PrPC is implicated in the morphogenesis of the skeletal muscle of adult mice. PrPC accomplished this task by modulating signaling pathways central to the myogenic process, in particular the p38 kinase pathway. The possibility that PrPC acts in cell signaling has already been suggested after in vitro studies. Using our in vivo approach, we have instead provided proof of the physiologic relevance of PrPC commitment in signaling events, and that PrPC likely performed the task by controlling the activity of the enzyme (TACE) secreting the signaling TNFα molecule. After a brief summary of our data, here we will discuss the suggestion, arising from our and other recent findings, implying that regulation of TACE, and of other members of the protease family TACE belongs to, may be exploited by PrPC in different cell contexts. Notably, this advancement of knowledge on PrPC physiology could also shed light on the defense mechanisms against the onset of a more common neurodegenerative disorder than prion disease, such as Alzheimer disease.
authors.affiliation: Department of Biological Chemistry, University of Padova, Padova, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Stella
authors.forename: Maria Lina
authors.initials: ML
authors.lastname: Massimino
authors.forename: M Catia
authors.initials: MC
authors.lastname: Sorgato
authors.forename: Alessandro
authors.initials: A
authors.lastname: Bertoli
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism*; D000072198:ADAM17 Protein; D000544:Alzheimer Disease / Q000378:metabolism; D000818:Animals; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism; D018621:PrPC Proteins / Q000378:metabolism*; D017096:Prion Diseases / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D018621:PrPC Proteins; D020033:Protein Isoforms; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606463:Adam17 protein, mouse