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Prion diseases are transmissible spongiform encephalopathies (TSEs), attributed to conformational conversion of the cellular prion protein (PrP C ) into an abnormal conformer that accumulates in the brain. Understanding the pathogenesis of TSEs requires the identification of functional properties of PrP C . Here we examine the physiological functions of PrP C at the systemic, cellular, and molecular level. Current data show that both the expression and the engagement of PrP C with a variety of ligands modulate the following: 1 ) functions of the nervous and immune systems, including memory and inflammatory reactions; 2 ) cell proliferation, differentiation, and sensitivity to programmed cell death both in the nervous and immune systems, as well as in various cell lines; 3 ) the activity of numerous signal transduction pathways, including cAMP/protein kinase A, mitogen-activated protein kinase, phosphatidylinositol 3-kinase/Akt pathways, as well as soluble non-receptor tyrosine kinases; and 4 ) trafficking of PrP C both laterally among distinct plasma membrane domains, and along endocytic pathways, on top of continuous, rapid recycling. A unified view of these functional properties indicates that the prion protein is a dynamic cell surface platform for the assembly of signaling modules, based on which selective interactions with many ligands and transmembrane signaling pathways translate into wide-range consequences upon both physiology and behavior. 1 Not to be confounded with the laminin receptor precursor, LRP.

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Physiology of the Prion Protein

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  • Publisher American Physiological Society
  • Copyright Copyright © 2011 the American Physiological Society
  • ISSN 0031-9333
  • eISSN 1522-1210
  • D.O.I. 10.1152/physrev.00007.2007
  • Publisher site Get PDF  

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