Coenzyme Q10 inhibits mitochondrial complex-1 down-regulation and nuclear factor-kappa B activation.
We have used control-homozygous weaver mutant, and -heterozygous weaver mutant mice in order to explore the basic molecular mechanism of neurodegeneration and the neuroprotective potential of coenzyme Q(10). Homozygous weaver mutant mice exhibited progressive neurodegeneration in the hippocampus, striatum, and cerebellum, and a reduction in the striatal levels of dopamine and coenzyme Qs (Q(9) and Q(10)) without any significant changes in norepinephrine and serotonin. Mitochondrial complex-1 was down regulated; whereas nuclear factor-kappa B was up regulated in homozygous weaver mutant mice. Rotenone inhibited complex-1, enhanced nuclear factor-kappa B, and caused apoptosis in human dopaminergic (SK-N-SH) neurons; whereas nuclear factor-kappa B antibody suppressed rotenone-induced apoptosis, suggesting that enhancing coenzyme Q(10) synthesis and suppressing the induction of NF-kappa B, may provide neuroprotection.
Ebadi
M
M
Center of Excellence For Neurosciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, North Dakota, USA. mebadi@medicine.nodak.edu
Sharma
S K
SK
Wanpen
S
S
Amornpan
A
A
D000375:Aging / Q000502:physiology; D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism; D001835:Body Weight; D045744:Cell Line, Tumor; D002490:Central Nervous System / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003067:Coenzymes; D053938:DNA Fragmentation; D015536:Down-Regulation / Q000187:drug effects*; D042967:Electron Transport Complex I / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008817:Mice, Mutant Strains; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*
D015306:Biogenic Monoamines; D003067:Coenzymes; D016328:NF-kappa B; D012333:RNA, Messenger; D014451:Ubiquinone; D042967:Electron Transport Complex I; C024989:coenzyme Q10