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Combination therapy with Coenzyme Q 10 and creatine produces additive neuroprotective effects in models of Parkinson’s and Huntington’s Diseases
Author(s) -
Yang Lichuan,
Calingasan Noel Y.,
Wille Elizabeth J.,
Cormier Kerry,
Smith Karen,
Ferrante Robert J.,
Flint Beal M.
Publication year - 2009
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2009.06074.x
Subject(s) - neuroprotection , parkinson's disease , huntington's disease , creatine , medicine , neuroscience , pharmacology , psychology , disease
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 α‐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.