title: Combination therapy with coenzyme Q10 and creatine produces additive neuroprotective effects in models of Parkinson's and Huntington's diseases.
abstract: Coenzyme Q(10) (CoQ(10)) and creatine are promising agents for neuroprotection in neurodegenerative diseases via their effects on improving mitochondrial function and cellular bioenergetics and their properties as antioxidants. We examined whether a combination of CoQ(10) with creatine can exert additive neuroprotective effects in a MPTP mouse model of Parkinson's disease, a 3-NP rat model of Huntington's disease (HD) and the R6/2 transgenic mouse model of HD. The combination of the two agents produced additive neuroprotective effects against dopamine depletion in the striatum and loss of tyrosine hydroxylase neurons in the substantia nigra pars compacta (SNpc) following chronic subcutaneous administration of MPTP. The combination treatment resulted in significant reduction in lipid peroxidation and pathologic alpha-synuclein accumulation in the SNpc neurons of the MPTP-treated mice. We also observed additive neuroprotective effects in reducing striatal lesion volumes produced by chronic subcutaneous administration of 3-NP to rats. The combination treatment showed significant effects on blocking 3-NP-induced impairment of glutathione homeostasis and reducing lipid peroxidation and DNA oxidative damage in the striatum. Lastly, the combination of CoQ(10) and creatine produced additive neuroprotective effects on improving motor performance and extending survival in the transgenic R6/2 HD mice. These findings suggest that combination therapy using CoQ(10) and creatine may be useful in the treatment of neurodegenerative diseases such as Parkinson's disease and HD.
authors.affiliation: Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York-Presbyterian Hospital, New York, New York 10021, USA.
authors.forename: Lichuan
authors.initials: L
authors.lastname: Yang
authors.forename: Noel Y
authors.initials: NY
authors.lastname: Calingasan
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Wille
authors.forename: Kerry
authors.initials: K
authors.lastname: Cormier
authors.forename: Karen
authors.initials: K
authors.lastname: Smith
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Ferrante
authors.forename: M Flint
authors.initials: MF
authors.lastname: Beal
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D000704:Analysis of Variance; D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003401:Creatine / Q000627:therapeutic use*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D004359:Drug Therapy, Combination; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D006816:Huntington Disease / Q000139:chemically induced / Q000188:drug therapy*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009574:Nitro Compounds; D010300:Parkinson Disease / Q000188:drug therapy* / Q000209:etiology; D011422:Propionates; D051381:Rats; D011917:Rats, Inbred Lew; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D051844:alpha-Synuclein / Q000378:metabolism
chemical_list: D018696:Neuroprotective Agents; D009574:Nitro Compounds; D011422:Propionates; D051844:alpha-Synuclein; D014451:Ubiquinone; D008315:Malondialdehyde; D000080242:8-Hydroxy-2'-Deoxyguanosine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase; C024989:coenzyme Q10; D003849:Deoxyguanosine; D005978:Glutathione; D003401:Creatine; C015392:3-nitropropionic acid; D019803:Glutathione Disulfide; D004298:Dopamine