Evaluation of coenzyme Q as an antioxidant strategy for Alzheimer's disease.
Increasing evidence suggests that Alzheimer's disease (AD) is associated with oxidative damage that is caused in part by mitochondrial dysfunction. Here we investigated the feasibility of modifying Alzheimer pathology with the mitochondrial antioxidant coenzyme Q (CoQ). Exogenous CoQ protected MC65 neuroblastoma cells from amyloid-beta protein precursor C-terminal fragment (APP CTF)-induced neurotoxicity in a concentration dependent manner, with concentrations of 6.25 microM and higher providing near complete protection. Dietary supplementation with CoQ at a dose of 10 g/kg diet to C65/Bl6 mice for one month significantly suppressed brain protein carbonyl levels, which are markers of oxidative damage. Treatment for one month with 2 g lovastatin/kg diet, which interferes with CoQ synthesis, resulted in a significant lowering of brain CoQ10 levels. Mitochondrial energetics (brain ATP levels and mitochondrial membrane potential) were unaffected by either CoQ or lovastatin treatment. Our results suggest that oral CoQ may be a viable antioxidant strategy for neurodegenerative disease. Our data supports a trial of CoQ in an animal model of AD in order to determine whether a clinical trial is warranted.
Wadsworth
Teri L
TL
Department of Neurology, Oregon Health & Science University, Portland, OR 97239-3098, USA. wadswort@ohsu.edu
Bishop
James A
JA
Pappu
Anuradha S
AS
Woltjer
Randall L
RL
Quinn
Joseph F
JF
D000255:Adenosine Triphosphate / Q000378:metabolism; D000544:Alzheimer Disease / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000633:toxicity; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D045744:Cell Line, Tumor; D019587:Dietary Supplements; D005260:Female; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D014451:Ubiquinone / Q000627:therapeutic use*
D016564:Amyloid beta-Protein Precursor; D000975:Antioxidants; D014451:Ubiquinone; D000255:Adenosine Triphosphate