Role of lipid rafts in the processing of the pathogenic prion and Alzheimer's amyloid-beta proteins.
The conformational conversion of the cellular form of the prion protein (PrP C) into the infectious form (PrP Sc) and the proteolytic processing of the amyloid-beta (Abeta) peptide are central pathogenetic events in the prion diseases and Alzheimer's disease, respectively. Cholesterol- and sphingolipid-rich lipid rafts have emerged as important sites for the conversion of PrP C into PrP Sc, and for the proteolytic production, degradation and aggregation of Abeta. Here, we discuss these findings and their implications for our understanding of these disease processes. In addition, the potential for rafts as sites for therapeutic intervention in prion diseases and Alzheimer's disease is considered.
Taylor
David R
DR
Proteolysis Research Group, Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, and Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds LS2 9JT, UK.
Hooper
Nigel M
NM
D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D006801:Humans; D021962:Membrane Microdomains / Q000378:metabolism*; D008954:Models, Biological; D017096:Prion Diseases / Q000378:metabolism*; D011328:Prions / Q000378:metabolism*