Fishing for Prion Protein Function 英文参考文献.docVIP

Primer Fishing for Prion Protein Function Roberto Chiesa*, David A. Harris* T he prion protein (PrP) is a membrane-anchored, neuronal glycoprotein whose normal function is uncertain, but which plays a crucial role in prion diseases, a class of fatal neurodegenerative disorders of humans and animals [1]. Bovine spongiform encephalopathy (“mad cow disease”) and kuru, which are transmitted by eating contaminated tissues, are the best known examples of these disorders, which also occur in inherited and sporadic forms. In prion diseases, the normal, endogenous form of Although PrP knockout mice display no major anatomical or developmental defects, a bewildering variety of subtle abnormalities have been described in these mice (reviewed in [12]). These include altered circadian rhythms [13] and olfaction [14], abnormalities in neuronal transmission and electrical activity [15], defective proliferation and differentiation of neural precursor cells [16] and hematopoietic stem cells [17], increased sensitivity to hypoxia, ischemia, and seizures [18], and enhanced resistance to microbial infections [19]. Although intriguing, none of these reported abnormalities has provided a PrP (PrP C ) undergoes transformation to a conformationally ) that accumulates in the brain altered version (PrP Sc as sticky, insoluble aggregates. This process leads to definitive clue to the normal function of PrP Studies on the cell biology of PrP have also failed to provide an unequivocal lead. Similar to other membrane glycoproteins, PrP is synthesized in the rough endoplasmic reticulum, transits the Golgi, and is delivered to the cell surface, where it resides in lipid rafts [20]. Some PrP C . neuronal dysfunction and progressive neurodegeneration, for which there is no effective treatment. Unlike other neurodegenerative disorders like Alzheimer’s disease that are also due to protein misfolding, prion diseases are unique because they are transmissible. Prion propagation occurs by C C C an unus