Therapeutic effects of coenzyme Q10 (CoQ10) and reduced CoQ10 in the MPTP model of Parkinsonism.
Coenzyme Q10 (CoQ10) is a promising agent for neuroprotection in neurodegenerative diseases. We tested the effects of various doses of two formulations of CoQ10 in food and found that administration in the diet resulted in significant protection against loss of dopamine (DA), which was accompanied by a marked increase in plasma concentrations of CoQ10. We further investigated the neuroprotective effects of CoQ10, reduced CoQ10 (ubiquinol), and CoQ10 emulsions in the (MPTP) model of Parkinson's disease (PD). We found neuroprotection against MPTP induced loss of DA using both CoQ10, and reduced CoQ10, which produced the largest increases in plasma concentrations. Lastly, we administered CoQ10 in the diet to test its effects in a chronic MPTP model induced by administration of MPTP by Alzet pump for 1 month. We found neuroprotective effects against DA depletion, loss of tyrosine hydroxylase neurons and induction of alpha-synuclein inclusions in the substantia nigra pars compacta. The finding that CoQ10 is effective in a chronic dosing model of MPTP toxicity, is of particular interest, as this may be more relevant to PD. These results provide further evidence that administration of CoQ10 is a promising therapeutic strategy for the treatment of PD.
Cleren
Carine
C
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York-Presbyterian Hospital, New York, New York 10021, USA.
Yang
Lichuan
L
Lorenzo
Beverly
B
Calingasan
Noel Y
NY
Schomer
Andrew
A
Sireci
Anthony
A
Wille
Elizabeth J
EJ
Beal
M Flint
MF
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D000821:Animal Feed; D000818:Animals; D003067:Coenzymes / Q000378:metabolism / Q000494:pharmacology; D004195:Disease Models, Animal; D004298:Dopamine / Q000502:physiology; D004347:Drug Interactions; D008297:Male; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology; D009498:Neurotoxins / Q000494:pharmacology; D010084:Oxidation-Reduction; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D014815:Vitamins / Q000378:metabolism / Q000494:pharmacology*
D003067:Coenzymes; D018696:Neuroprotective Agents; D009498:Neurotoxins; D014815:Vitamins; D014451:Ubiquinone; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; C024989:coenzyme Q10; D004298:Dopamine