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Evaluation of coenzyme Q as an antioxidant strategy for Alzheimer's disease.

Journal of Alzheimer's disease : JAD (2008-06-19)
Teri L Wadsworth, James A Bishop, Anuradha S Pappu, Randall L Woltjer, Joseph F Quinn
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Mitochondria Isolation Kit, sufficient for 50 applications (2-5 x 107 cells), isolation of enriched mitochondrial fraction from cells
Supelco
Butylated Hydroxytoluene, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Sodium azide, BioXtra
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Sodium azide, ReagentPlus®, ≥99.5%
Sigma-Aldrich
Sodium azide, BioUltra, ≥99.5% (T)
Sigma-Aldrich
Butylated hydroxytoluene, ≥99%, FCC, FG
Sigma-Aldrich
Sodium azide, purum p.a., ≥99.0% (T)
Sigma-Aldrich
Mitochondria Isolation Kit, sufficient for 10-20 g (animal tissue), sufficient for 50 assays (2 mL), isolation of enriched mitochondrial fraction from animal tissues