title: Oxidative stress in Niemann-Pick disease, type C.
abstract: Niemann-Pick disease, type C (NPC) is a neurodegenerative lysosomal storage disorder due to impaired intracellular cholesterol and lipid transport. Increased oxidative stress has been reported in human NPC1 mutant fibroblasts and in tissues from Npc1 mutant mice. However, oxidative stress in NPC patients has not been established. In this study, we demonstrated increased oxidative stress in NPC patients. Evaluation of serum from 37 NPC patients, compared to control values, showed significant decreases (p<.01) in both the fraction of reduced coenzyme Q10 (CoQ10) and trolox equivalent antioxidant capacity (TEAC). Both findings are consistent with increased oxidative stress in NPC. Supplementation with CoQ10 was not effective in correcting the decreased fraction of reduced CoQ10. Increased oxidative stress may be a contributing factor to the pathology of NPC, and demonstration of increased oxidative stress in NPC patients provides both a rationale and the biomarkers necessary to test the efficacy of antioxidant therapy in NPC.
authors.affiliation: Program in Developmental Endocrinology and Genetics, NICHD, NIH, DHHS, Bethesda, MD 20892, USA.
authors.forename: Rao
authors.initials: R
authors.lastname: Fu
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Yanjanin
authors.forename: Simona
authors.initials: S
authors.lastname: Bianconi
authors.forename: William J
authors.initials: WJ
authors.lastname: Pavan
authors.forename: Forbes D
authors.initials: FD
authors.lastname: Porter
mesh_terms: D017485:1-Deoxynojirimycin / Q000031:analogs & derivatives / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007223:Infant; D008875:Middle Aged; D052556:Niemann-Pick Disease, Type C / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D018384:Oxidative Stress / Q000235:genetics*; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use
chemical_list: D014451:Ubiquinone; D017485:1-Deoxynojirimycin; C059896:miglustat; C024989:coenzyme Q10