BSE and vCJD cause disturbance to uric acid levels.
Bovine spongiform encephalopathy (BSE) and variant Creutzfeldt-Jakob disease (vCJD) are two new members of the family of neurodegenerative conditions termed prion diseases. Oxidative damage has been shown to occur in prion diseases and is potentially responsible for the rapid neurodegeneration that is central to the pathogenesis of these diseases. An important nonenzymatic antioxidant in the brain is uric acid. Analysis of uric acid in the brain and cerebrospinal fluid (CSF) of cases of BSE and CJD showed a specific reduction in CSF levels for both BSE and variant CJD, but not sporadic CJD. Further studies based on cell culture experiments suggested that uric acid in the brain was produced by microglia. Uric acid was also shown to inhibit neurotoxicity of a prion protein peptide, production of the abnormal prion protein isoform (PrP(Sc)) by infected cells, and polymerization of recombinant prion protein. These findings suggest that changes in uric acid may aid differential diagnosis of vCJD. Uric acid could be used to inhibit cell death or PrP(Sc) formation in prion disease.
Lekishvili
Tamuna
T
Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath, BA2 7AY, UK.
Sassoon
Judyth
J
Thompsett
Andrew R
AR
Green
Alison
A
Ironside
James W
JW
Brown
David R
DR
D000818:Animals; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D007562:Creutzfeldt-Jakob Syndrome / Q000134:cerebrospinal fluid / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D016643:Encephalopathy, Bovine Spongiform / Q000134:cerebrospinal fluid / Q000378:metabolism*; D006801:Humans; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000494:pharmacology; D018620:PrPSc Proteins / Q000096:biosynthesis; D011328:Prions / Q000037:antagonists & inhibitors / Q000494:pharmacology; D014527:Uric Acid / Q000032:analysis / Q000378:metabolism* / Q000494:pharmacology
D010446:Peptide Fragments; D018620:PrPSc Proteins; D011328:Prions; C082632:prion protein (106-126); D014527:Uric Acid