期刊
FRONTIERS IN BIOSCIENCE-LANDMARK
卷 16, 期 -, 页码 151-168出版社
FRONTIERS IN BIOSCIENCE INC
DOI: 10.2741/3681
关键词
Prion; Lipid Raft; Cholesterol; Sphingolipid; Caveolae; Review
资金
- Australian Government, National Health and Medical Research Council [567123]
- Medical Research Council of Great Britain
- Wellcome Trust
- Medical Research Council [G0802189] Funding Source: researchfish
- MRC [G0802189] Funding Source: UKRI
The conformational conversion of the cellular prion protein, PrPC, to the misfolded isoform PrPSc is the central pathogenic event in the uniquely transmissible neurodegenerative prion diseases. As both PrPC and PrPSc are associated with membranes, the nature of the membrane microenvironment may well play a significant role in both the conformational conversion process as well as the normal functions of PrPC. Within the membrane are various microdomains, areas of distinct lipid and protein composition, the best studied of which are the cholesterol- and sphingolipid-rich lipid rafts. These domains are characterized biochemically by their relative resistance to solubilization in certain detergents at low temperature. In this article we review the evidence for the involvement of lipid rafts in the localization and trafficking of PrPC, in the cellular signaling, neuroprotective and metal binding functions of PrPC, and as sites for the conversion of PrPC to PrPSc and in cell-to-cell prion transmission.
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