title: Shedding light on prion disease.
abstract: Proteolytic processing regulates key processes in health and disease. The cellular prion protein (PrP(C)) is subject to at least 3 cleavage events, α-cleavage, β-cleavage and shedding. In contrast to α- and β-cleavage where there is an ongoing controversy on the identity of relevant proteases, the metalloprotease ADAM10 represents the only relevant PrP sheddase. Here we focus on the roles that ADAM10-mediated shedding of PrP(C) and its pathogenic isoform (PrP(Sc)) might play in regulating their physiological and pathogenic functions, respectively. As revealed by our recent study using conditional ADAM10 knockout mice (Altmeppen et al., 2015), shedding of PrP seems to be involved in key processes of prion diseases. These aspects and several open questions arising from them are discussed. Increased knowledge on this topic can shed new light on prion diseases and other neurodegenerative conditions as well.
authors.affiliation: a Institute of Neuropathology; University Medical Center Hamburg-Eppendorf ; Hamburg , Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Glatzel
authors.forename: Luise
authors.initials: L
authors.lastname: Linsenmeier
authors.forename: Frank
authors.initials: F
authors.lastname: Dohler
authors.forename: Susanne
authors.initials: S
authors.lastname: Krasemann
authors.forename: Berta
authors.initials: B
authors.lastname: Puig
authors.forename: Hermann C
authors.initials: HC
authors.lastname: Altmeppen
mesh_terms: D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D018621:PrPC Proteins / Q000235:genetics / Q000378:metabolism; D017096:Prion Diseases / Q000235:genetics / Q000378:metabolism*
chemical_list: D018621:PrPC Proteins; D051722:ADAM Proteins
keywords: ADAM10; neurodegeneration; prion disease; proteolytic processing; shedding