There are many recognized neurological diseases, such as epilepsy, AD, PD, MS, stroke, autosomal recessive cerebellar ataxia 2 (ARCA2), Leber’s hereditary optic neuropathy (LHON) and spinocerebellar ataxia autosomal recessive 9 (SCAR9). Coenzyme Q10 (CoQ10 …ubiquinone), exerts neuroprotective effects against neuronal damage, has antioxidant, anti-inflammatory effects, plays a role in energy production and mitochondrial stabilization, mechanisms by which it exerts its neuroprotective effects.
The prevalence of age-related disorders has increased, and coenzyme Q10 is a potent neuroprotective agent in neurodegenerative disorders.
Its levels decrease in the brain and different tissues with age and has an effective therapeutic role in age-related neurodegenerative disorders.
CoQ10 deficiencies are genetically and clinically heterogeneous. The syndrome has five main clinical phenotypes:
- cerebellar ataxia
- severe infantile multisystem disease
- Encephalomyopathy
- isolated myopathy
- nephrotic syndrome.
In some cases, pathogenic mutations are observed in genes related to its biosynthesis (primary deficiencies) or in those not directly related to its biosynthesis (secondary deficiencies). The pathogenesis of primary CoQ10 deficiencies has been linked to defects in the respiratory chain, ROS generation, and apoptosis. Secondary deficiency is probably related to hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) in hypercholesterolemia. Dietary contributions of CoQ10 are very small, but supplementation [side effects nausea] can increase plasma levels. CoQ10 is safe up to 1,200 mg/day and has a role in reducing INR in patients on warfarin that is not significant in patients on stable, long-term warfarin therapy with 100 mg CoQ10 for 4 weeks.
Mitochondrial cells have CoQ10 levels with oxidized (ubiquinone) and reduced ubiquinol. Ubiquinol is an antioxidant and is oxidized to ubiquinone in free radical reactions, limiting LPO. Ubiquinol is the reduced form of CoQ10, associated with antioxidant function. Ubiquinol activates endogenous systems (tocopherol and ascorbate). The ratio of oxidized to reduced CoQ10 species is a biomarker for oxidative stress in vivo.
Therefore, tissues and cells should have molecular mechanisms to recover their active form.CoQ10 is a critical cofactor for ATP production in the electron transport chain (ETC). This coenzyme provides electrons from complexes I and II and transfers them to complex III and is an important endogenous antioxidant is a critical component of the mitochondrial respiratory chain. Its antioxidant function is due to the reduced form of ubiquinol.Thus, a CoQ10 deficiency can cause certain diseases due to failure in energy metabolism and a compromise of cellular antioxidant defense. Based on these findings, the antioxidant effect of CoQ10 reduces the function of inflammatory factors and proves to be a potent neuroprotective agent in neurotoxicity. many in vitro studies and also in animal models of neurological diseases.
SOURCE: Neurosci. 2023
