In the amyloidogenic pathway, the APP (amyloid precursor protein) is proteolytically processed by the β- and γ-secretases to release the Aβ (amyloid-β) peptide that is neurotoxic and aggregates in the brains of patients suffering from Alzheimer's disease. In the non-amyloidogenic pathway, APP is cleaved by α-secretase within the Aβ domain, precluding deposition of intact Aβ peptide. The cellular form of the PrPC (prion protein) undergoes reactive oxygen species-mediated β-cleavage within the copper-binding octapeptide repeats or, alternatively, α-cleavage within the central hydrophobic neurotoxic domain. In addition, PrPC is shed from the membrane by the action of a zinc metalloprotease. Members of the ADAM (a disintegrin and metalloproteinase) family of zinc metalloproteases, notably ADAM10 and TACE (ADAM17) display α-secretase activity towards APP and appear to be responsible for the α-cleavage of PrPC. The amyloidogenic cleavage of APP by the β- and γ-secretases appears to occur preferentially in cholesterol-rich lipid rafts, while the conversion of PrPC into the infectious form PrPSc also appears to occur in these membrane domains.
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Conference Article|
April 01 2005
Roles of proteolysis and lipid rafts in the processing of the amyloid precursor protein and prion protein
N.M. Hooper
N.M. Hooper
1
1Proteolysis Research Group, School of Biochemistry and Microbiology, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds LS2 9JT, U.K.
1email n.m.hooper@leeds.ac.uk
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Publisher: Portland Press Ltd
Received:
November 01 2004
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2005 The Biochemical Society
2005
Biochem Soc Trans (2005) 33 (2): 335–338.
Article history
Received:
November 01 2004
Citation
N.M. Hooper; Roles of proteolysis and lipid rafts in the processing of the amyloid precursor protein and prion protein. Biochem Soc Trans 1 April 2005; 33 (2): 335–338. doi: https://doi.org/10.1042/BST0330335
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