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.