Affiliations: [a] Department of Neurology, Oregon Health & Science University, Portland, OR, USA | [b] Department of Medicine, Oregon Health & Science University, Portland, OR, USA | [c] Department of Pathology, Oregon Health & Science University, Portland, OR, USA | [d] Portland Veteran's Affairs Medical Center P3 R&D, Portland, OR, USA
Correspondence:
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Corresponding author: Teri L. Wadsworth, Department of Neurology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239-3098, USA. Tel.: +1 503 494 7234; Fax: +1 503 494 7499; E-mail: [email protected].
Note: [] Communicated by Paula I. Moreira.
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-β protein precursor C-terminal fragment (APP CTF)-induced neurotoxicity in a concentration dependent manner, with concentrations of 6.25 μM 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.
Keywords: Alzheimer's disease, coenzyme Q, lovastatin, MC65, Tg2576
