Prion proteins meet protein quality control.
Recent work on transmissible spongiform encephalopathies (TSEs) suggests a role for protein quality-control mechanisms in both prion protein aggregation and pathogenesis. Cytosolic accumulation of prion protein seems to be neurotoxic and might occur when proteasome function is compromised and quality control is overwhelmed. These findings are discussed in the light of other studies linking proteasome inhibition and neurodegeneration.
Dimcheff
Derek E
DE
Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases/NIH, Hamilton, MT 59840, USA. ddimcheff@nih.gov
Portis
John L
JL
Caughey
Byron
B
D000818:Animals; D003546:Cysteine Endopeptidases / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D009097:Multienzyme Complexes / Q000378:metabolism; D009410:Nerve Degeneration / Q000378:metabolism / Q000503:physiopathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D018621:PrPC Proteins / Q000378:metabolism*; D018620:PrPSc Proteins / Q000378:metabolism*; D017096:Prion Diseases / Q000378:metabolism* / Q000503:physiopathology; D046988:Proteasome Endopeptidase Complex; D017510:Protein Folding; D021381:Protein Transport / Q000502:physiology
D009097:Multienzyme Complexes; D018621:PrPC Proteins; D018620:PrPSc Proteins; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex