TABLE 1.
Principal studies describing neuroprotective molecular mechanisms of coenzyme Q10 (CoQ10) and citicoline.
| Mechanism | References | Outcomes |
| Bcl family proteins regulation | (52) | Neuroprotection provided by citicoline is due to an increased retinal expression of the apoptotic regulating protein Bcl-2 possibly mimicking brain-derived neurotrophic factor. |
| (41) | CoQ10 promoted RGC survival in glaucomatous DBA/2J mice. CoQ10 significantly decreased Bax protein expression, that is a proapoptotic member of the Bcl-2 family, essential in many pathways of apoptosis. | |
| Excitotoxicity regulation | (53) | Morphometric analysis showed a significant reduction in inner nuclear and inner plexiform layers thicknesses and ganglion cell loss after kainic acid injection, but the rate of thinning in retinal layers was reduced after citicoline treatment. |
| (54) | Citicoline has a neuroprotective effect on retinal damage due to kainic acid-induced neurotoxicity. | |
| (42) | CoQ10 promotes RGC survival by inhibiting oxidative stress, glutamate excitotoxicity, and activation of the Bax and Bad–mediated apoptotic pathway and by preserving mtDNA content and Tfam/OXPHOS complex IV protein expression in glaucomatous DBA/2J mice. | |
| Caspases regulation | (52) | Citicoline can reduce the expression of active forms of caspases-9 and-3 regulating apoptosis. |
| Effect on mitochondria | (52) | Citicoline increase the availability of nucleotides essential for the synthesis of membrane phospholipids and enhances bioenergetics and phospholipid membrane turnover in the brain. |
| (34) | CoQ10 promote mitofilin protein expression, providing protection to the mitochondria, and ultimately OXPHOS capacity against oxidative stress. | |
| (44) | CoQ10 has bioenergetic properties. CoQ10 reduction/oxidation cycles transfer protons across the membrane forming a proton gradient essential to producing ATP. | |
| Neurotransmitters system stimulation | (56) | Citicoline reinforces dopaminergic transmission in the retina |
| Membrane integrity maintenance | (46) | CDP-choline is a precursor of glycerophospholipid phosphatidylcholine which is an essential phospholipid for the maintenance of intracellular and extracellular membranes of eukaryotic organisms; these molecules are of particular relevance in surveying neuron homeostasis and functionality, by serving membranes turnover, synaptic plasticity, and neurotransmission. |
| (60) | Citicoline leads to the formation of phosphatidylcholine, which is an important component of neuronal membranes and is imperative to the membrane integrity of the retinal ganglion cells. | |
| Anti-inflammatory properties | (46) | Citicoline was found to be protective in transient cerebral ischemia through the inhibition of phospholipase A2. |
| (62) | CoQ10 induced a significant reduction of TNF-α level, lessening the production of pro-inflammatory cytokines and lowering the production of macrophage inflammatory protein-1 alpha. | |
| Cerebral blood flow improvement | (60) | Citicoline inducing calcium release from endothelial cells improves endothelial function leading to improved microvasculature and better blood flow. |
| (64) | Prescription of citicoline for treatment of acute ischemic stroke is associated with hemodynamic changes in cerebral arteries. | |
| (63) | Citicoline is well tolerated and improves cognitive performance, cerebral blood perfusion and the brain bioelectrical activity pattern in Alzheimer’s disease. | |
| Mutual beneficial effect on molecules metabolism | (65) | Ubiquinone is necessary for the L-3-glycerophosphate oxidase of pig brain mitochondria. |
| (58) | Choline oxidization is restored by the addition of ubiquinone-2 or ubiquinone-10 to the oxidase assay medium. CoQ10 was found to increase the choline oxidase activity in ubiquinone-depleted mitochondria. | |
| (66) | Solubilized choline dehydrogenase is capable to reduce ubiquinone. | |
| (68) | CoQ10 showed a neuroprotective activity, in the case of choline depletion, by inhibiting the release of glutamate in rat cerebrocortical nerve terminals. |