NR ASPL
AU Hooper,N.M.
TI Roles of proteolysis and lipid rafts in the processing of the amyloid precursor protein and prion protein
QU Biochemical Society Transactions 2005 Apr; 33(2): 335-8
PT journal article; review; review, tutorial
AB In the amyloidogenic pathway, the APP (amyloid precursor protein) is proteolytically processed by the beta- and gamma-secretases to release the Abeta (amyloid-beta) 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 alpha-secretase within the Abeta domain, precluding deposition of intact Abeta peptide. The cellular form of the PrPc (prion protein) undergoes reactive oxygen species-mediated beta-cleavage within the copper-binding octapeptide repeats or, alternatively, alpha-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 alpha-secretase activity towards APP and appear to be responsible for the alpha-cleavage of PrPc. The amyloidogenic cleavage of APP by the beta- and gamma-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.
ZR 50
MH Alzheimer Disease/metabolism; Amyloid beta-Protein Precursor/*metabolism; Animals; Cholesterol/metabolism; Humans; Membrane Microdomains/chemistry/*metabolism; Prions/*metabolism; *Protein Processing, Post-Translational; Research Support, Non-U.S. Gov't
AD Proteolysis Research Group, School of Biochemistry and Microbiology, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds LS2 9JT, UK. n.m.hooper@leeds.ac.uk
SP englisch
PO England