Taylor David R, Hooper Nigel M
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.
Semin Cell Dev Biol. 2007 Oct;18(5):638-48. doi: 10.1016/j.semcdb.2007.07.008. Epub 2007 Jul 24.
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.
朊病毒蛋白的细胞形式(PrP C)向感染性形式(PrP Sc)的构象转变以及β淀粉样蛋白(Aβ)肽的蛋白水解加工分别是朊病毒病和阿尔茨海默病的核心致病事件。富含胆固醇和鞘脂的脂筏已成为PrP C转变为PrP Sc以及Aβ蛋白水解产生、降解和聚集的重要场所。在此,我们讨论这些发现及其对我们理解这些疾病过程的意义。此外,还考虑了脂筏作为朊病毒病和阿尔茨海默病治疗干预靶点的潜力。