The consequences of pathogenic mutations to the human prion protein.
Prion diseases, in which the conformational transition of the native prion protein (PrP) to a misfolded form causes aggregation and subsequent neurodegeneration, have fascinated the scientific community as this transmissible disease appears to be purely protein-based. Disease can arise due to genetic factors only. At least 30 single point mutations have been indicated to cause disease in humans. Somehow, these mutations must influence the stability, processing and/or cellular interactions of PrP, such that aggregation can occur and disease develops. In this review, the current evidence for such effects of single point mutations is discussed, indicating that PrP can be affected in many different ways, although questions remain about the mechanism by which mutations cause disease.
van der Kamp
Marc W
MW
Department of Bioengineering, University of Washington, Seattle, WA 98195-5013, USA.
Daggett
Valerie
V
D006801:Humans; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D017354:Point Mutation; D011328:Prions / Q000235:genetics* / Q000378:metabolism; D017510:Protein Folding; D017434:Protein Structure, Tertiary
D011328:Prions