title: Roles of endoproteolytic α-cleavage and shedding of the prion protein in neurodegeneration.
abstract: The cellular prion protein (PrP(C)) plays important roles in neurodegenerative diseases. First, it is the well-established substrate for the conformational conversion into its pathogenic isoform (PrP(Sc)) giving rise to progressive and fatal prion diseases. Moreover, several recent reports highlight important roles of PrP(C) in other neurodegenerative conditions such as Alzheimer's disease. Since PrP(C) is subject to proteolytic processing, here we discuss the two main cleavage events under physiological conditions, α-cleavage and shedding. We focus on how these cleavages and the resulting fragments may impact prion diseases as well as other neurodegenerative proteinopathies. Finally, we discuss the recently identified sheddase of PrP(C), namely the metalloprotease ADAM10, with regard to therapeutic potential against neurodegenerative diseases.
authors: Institute of Neuropathology, University Medical Center HH-Eppendorf, Hamburg, Germany. h.altmeppen@uke.de
authors: Hermann C
authors: HC
authors: Altmeppen
authors: Johannes
authors: J
authors: Prox
authors: Berta
authors: B
authors: Puig
authors: Frank
authors: F
authors: Dohler
authors: Clemens
authors: C
authors: Falker
authors: Susanne
authors: S
authors: Krasemann
authors: Markus
authors: M
authors: Glatzel
mesh_terms: D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism*; D000072197:ADAM10 Protein; D000544:Alzheimer Disease / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D018621:PrPC Proteins / Q000235:genetics / Q000378:metabolism*; D018620:PrPSc Proteins / Q000235:genetics / Q000378:metabolism*; D017096:Prion Diseases / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D011487:Protein Conformation; D017510:Protein Folding; D011499:Protein Processing, Post-Translational; D059748:Proteolysis; D015398:Signal Transduction
chemical_list: D016229:Amyloid beta-Peptides; D008565:Membrane Proteins; D018621:PrPC Proteins; D018620:PrPSc Proteins; D053829:Amyloid Precursor Protein Secretases; D051722:ADAM Proteins; D000072197:ADAM10 Protein; C491236:ADAM10 protein, human
keywords: ADAM10; Alzheimer's disease; neurodegeneration; neurotoxic oligomers; prion disease; prion protein; shedding; α-cleavage; β-amyloid