Co-enzyme Q10

CoQ10 is a lipophilic substance occurring in every cell. It plays a pivotal role to transport electrons from the complexes I and II to complex III, which is the cells power supply. Its reversible oxidation is the basis for its function as electron carrier. Reduced CoQ10 additionally functions as an intracellular antioxidant.

 

Mitochondrial protection

Evidence suggests a strong link between most of the neurological conditions and defects in the oxidative – reductive cycle (1,2). During the past few years CoQ10 has been used in different neurodegenerative diseases where a common biochemical feature is the evidence of oxidative stress and mitochondrial respiratory chain dysfunction. Mitochondria also play a central role in apoptotic cell death. The transport of high-energy electrons through the mitochondrial ETC is a necessary step for ATP production; also it is a source of reactive oxygen species (ROS) production. The accumulation of ROS can potentially damage bio-molecules, including lipids, proteins and nucleic acid (3). Damage to nDNA and mtDNA can have deleterious effects on post-mitotic cells such as neurons. Usually, the cell contains some defence mechanisms e.g. mitochondrial manganese superoxide dismutase, glutathione peroxidase for neutralizing the accumulated ROS.

 

Oxidative Stress

In normal situations CoQ10 is capable of accommodating the flux of ROS (4). CoQ10 may act by stabilizing the mitochondrial membrane when neuronal cells are subjected to oxidative stress (5,6). There is strong evidence supporting the role of oxidative stress and defective energy metabolism in the pathogenesis of many neurodegenerative disorders, such as Parkinson’s disease (PD), Huntington’s disease (HD), and Alzheimer disease (AD). The elevated levels of 8-hydroxy-2’- deoxyguanosine (8OHdG) in certain neurodegenerative disorders besides the elevated protein carbonyl formation and oxidized nitric oxide products with decreased glutathione peroxidase activity would suggest the role of oxidative disturbance in those disorders (7-9).

 

Neuroprotection

Jimenez-Jimenez et al. compared serum levels of CoQ10 and the CoQ10 /cholesterol ratio in patients with PD and matched controls (10). The CoQ10 /cholesterol ratio were correlated to the duration of disease. Other studies demonstrated an impaired electron transport or a higher need for reduced forms of CoQ in parkinsonian patients (11). Another study, examining concentrations of oxidized CoQ10 and reduced CoQ10 in the cerebrospinal fluid (CSF) of patients with PD found the percentage of oxidized/total CoQ10 in circulation was higher in untreated PD patients (12). The same group showed that the concentration of 8- OHdG in the CSF of PD patients was greater than in the CSF of controls (P < 0. 0001) and was positively correlated with the duration of illness. Moreover, the % CoQ10 was correlated with concentrations of 8-OHdG in the CSF of PD patients. These results suggest that both mitochondrial oxidative damage and oxidative DNA damage play important roles in the pathogenesis of early PD development (13-23).

Similarly, it is thought oxidative damage is the earliest event in AD (24). On investigating the possibility that mitochondrial oxidative damage, oxidative DNA damage or both contribute to the neurodegenerative process of AD, Isobe showed that 8-OHdG concentration in AD patients were higher, and positively correlated to disease duration (25). Multiple trials of idebenone form of CoQ10 in AD were performed in the 1990s, showing beneficial effects (26-28).

 

References

1 Littarru, G.P.; Tiano, L., Clinical aspects of coenzyme Q10: an update. Nutrition, 2010, 26, (3), 250-254.

2 Littarru, G.P.; Tiano, L., Clinical aspects of coenzyme Q10: an update. Curr Opin Clin Nutr Metab Care, 2005, 8, (6), 641-646.

3 Spindler, M.; Beal, M.F.; Henchcliffe, C., Coenzyme Q10 effects in neurodegenerative disease. Neuropsychiatr Dis Treat, 2009, 5, 597-610.

4 Mancuso, M.; Coppede, F.; Migliore, L.; Siciliano, G.; Murri, L., Mitochondrial dysfunction, oxidative stress and neurodegeneration. J Alzheimers Dis, 2006, 10, (1), 59-73.

5 Mancuso, M.; et al, Oxidative stress biomarkers in mitochondrial myopathies, basally and after cysteine donor supplementation. J Neurol, 2010, 257, (5), 774-781.

6 Linnane, A.W., Cellular coenzyme Q10 redox poise constitutes a major cell metabolic and gene regulatory system. Biogerontology, 2002, 3, (1-2), 3-6.

7 Cooper, J.M.; Schapira, A.H., Friedreich's Ataxia: disease mechanisms, antioxidant and Coenzyme Q10 therapy. Biofactors, 2003, 18, (1-4), 163-171.

8 Strong, M.J.; Pattee, G.L., Creatine and coenzyme Q10 in the treatment of ALS. Amyotroph Lateral Scler Other Motor Neuron Disord, 2000, 1 Suppl 4, 17-20.

9 Sohmiya, M.; Tanaka, M.; Suzuki, Y.; Tanino, Y.; Okamoto, K.; Yamamoto, Y., An increase of oxidized coenzyme Q-10 occurs in the plasma of sporadic ALS patients. J Neurol Sci, 2005, 228, (1), 49-53.

10 Jimenez-Jimenez, F.J.et al, Serum levels of coenzyme Q10 in patients with Parkinson's disease. J Neural Transm, 2000, 107, (2), 177-181.

11 Goetz, C.G.; et al, Placebo-associated improvements in motor function: comparison of subjective and objective sections of the UPDRS in early Parkinson's disease. Mov Disord, 2002, 17, (2), 283-288.

12 Isobe, C.; Murata, T.; Sato, C.; Terayama, Y., Increase of oxidized/total coenzyme Q-10 ratio in cerebrospinal fluid in patients with Parkinson's disease. J Clin Neurosci, 2007, 14, (4), 340-343.

13 Isobe, C.; Levels of reduced and oxidized coenzyme Q-10 and 8-hydroxy-2'-deoxyguanosine in the cerebrospinal fluid of patients with living Parkinson's disease. Neurosci Lett, 2010, 469, (1), 159-163.

14 Shults, C.W.; et al., Effects of coenzyme Q10 in early Parkinson disease: evidence of slowing of the functional decline. Arch Neurol, 2002, 59, (10), 1541-1550.

15 Shults, C.W.; Flint Beal, M.; Song, D.; Fontaine, D., Pilot trial of high dosages of coenzyme Q10 in patients with Parkinson's disease. Exp Neurol, 2004, 188, (2), 491-494.

16 Muller, T.; Buttner, T.; Gholipour, A.F.; Kuhn, W., Coenzyme Q10 supplementation provides mild symptomatic benefit in patients with Parkinson's disease. Neurosci Lett, 2003, 341, (3), 201-204.

17 Horstink, M.W.; van Engelen, B.G., The effect of coenzyme Q10 therapy in Parkinson disease could be symptomatic. Arch Neurol, 2003, 60, (8), 1170-1172; author reply 1172-1173.

18 Gibson, G.E.; et al., Reduced activities of thiamine-dependent enzymes in the brains and peripheral tissues of patients with Alzheimer's disease. Arch Neurol, 1988, 45, (8), 836-840.

19 Sheu, K.F.; et al., Abnormality of the alpha-ketoglutarate dehydrogenase complex in fibroblasts from familial Alzheimer's disease. Ann Neurol, 1994, 35, (3), 312-318.

20 Kanamori, T.; et al., Truncated product of the bifunctional DLST gene involved in biogenesis of the respiratory chain. Embo J, 2003, 22, (12), 2913-2923.

21 Hirai, K.; Aliev, G.; et al., Mitochondrial abnormalities in Alzheimer's disease. J Neurosci, 2001, 21, (9), 3017-3023.

22 Nunomura, A.; Perry, G.; et al., Oxidative damage is the earliest event in Alzheimer disease. J Neuropathol Exp Neurol, 2001, 60, (8), 759-767.

23 Isobe, C.; Abe, T.; Terayama, Y., Levels of reduced and oxidized coenzyme Q-10 and 8-hydroxy-2'-deoxyguanosine in the CSF of patients with Alzheimer's disease. J Neurol, 2010, 257, (3), 399-404.

24 Senin, U.; Parnetti, L.; Barbagallo-Sangiorgi, G.; et al Idebenone in senile dementia of Alzheimer type: a multicentre study. Arch Gerontol Geriatr, 1992, 15, (3), 249-260.

25 Bergamasco, B.; et al, Idebenone in the treatment of multi-infarct dementia: a randomised, double-blind, placebo controlled multicentre trial. Arch Gerontol Geriatr, 1992, 15, (3), 271-278.

26 Weyer, G.; Babej-Dolle, R.M.; Hadler, D.; Hofmann, S.; Herrmann, W.M., A controlled study of 2 doses of idebenone in the treatment of Alzheimer's disease. Neuropsychobiology, 1997, 36, (2), 73-82.

27 Gutzmann, H.; et al, Sustained efficacy and safety of idebenone in the treatment of Alzheimer's disease: update on a 2- year double-blind multicentre study. J Neural Transm Suppl, 1998, 54, 301-310.

28 Thal, L.J.; et al Idebenone treatment fails to slow cognitive decline in Alzheimer's disease. Neurology, 2003, 61, (11), 1498-1502.