2 RESEARCH ARTICLES
(1) There is a substantial body of literature, which has demonstrated that creatine has neuroprotective effects both in vitro and in vivo
(2) We carried out studies examining the efficacy of creatine as a neuroprotective agent in vivo.
(3) Creatine can protect against excitotoxic lesions produced by N-methyl-D: -aspartate.
(4) Creatine is neuroprotective against lesions produced by the toxins malonate and 3-nitropropionic acid (3-NP)
(5) Creatine produced dose-dependent neuroprotective effects against MPTP toxicity
– Creatine produced in a transgenic mouse model:
(1) an extension of survival
(2) improved motor performance
(3) a reduction in loss of motor neurons
PARKINSON’S & HUNTINGTON’S
(1) Creatine increases the brain levels of creatine and phosphocreatine
(2) Due to its neuroprotective effects, creatine is now in clinical trials for the treatment of Parkinson’s disease (PD) and HD.
(3) Creatine produced an extension of survival, as well as improved motor function, and a reduction in striatal atrophy in the R6/2 and the N-171-82Q transgenic mouse models of Huntington’s disease (HD), even when its administration was delayed until the onset of disease symptoms
(1) We recently examined the neuroprotective effects of a combination of CoQ10 with creatine against both MPTP and 3-NP toxicity
(2) CoQ and Creatine together produced additive neuroprotective effects in a chronic MPTP model, and it blocked the development of alpha-synuclein aggregates
(3) In the 3-NP model of HD, CoQ and creatine produced additive neuroprotective effects against the size of the striatal lesions
(4) In the R6/2 transgenic mouse model of HD, the combination of CoQ and creatine produced additive effects on improving survival
(1) Creatine may stabilize mitochondrial creatine kinase, and prevent activation of the mitochondrial permeability transition
(2) Creatine, however, was still neuroprotective in mice, which were deficient in mitochondrial creatine kinase
– Creatine, therefore, shows great promise in the treatment of a variety of neurodegenerative diseases
Combination Therapy with Coenzyme Q10 and Creatine Produces Additive Neuroprotective Effects in Models of Parkinson’s and Huntington’s Diseases – 2009
Lichuan Yang,1 Noel Y. Calingasan,1 Elizabeth J. Wille,1 Kerry Cormier,2,3 Karen Smith,2,3 Robert J. Ferrante,2,3 and M. Flint Beal
– Coenzyme Q10 (CoQ10) and creatine are promising agents for neuroprotection in neurodegenerative diseases via their effects on:
(1) improving mitochondrial function and cellular bioenergetics
(2) their properties as antioxidants.
– We examined whether a combination of CoQ10 with creatine can exert additive neuroprotective effects in a MPTP mouse model of Parkinson’s disease (PD), a 3-NP rat model of Huntington’s disease (HD) and the R6/2 transgenic mouse model of HD.
(1) 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.
(2) The combination treatment resulted in significant reduction in lipid peroxidation and pathologic α-synuclein accumulation in the SNpc neurons of the MPTP-treated mice.
(3) We also observed additive neuroprotective effects in reducing striatal lesion volumes produced by chronic subcutaneous administration of 3-NP to rats.
(4) 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.
(5) Lastly, the combination of CoQ10 and creatine produced additive neuroprotective effects on improving motor performance and extending survival in the transgenic R6/2 HD mice.
– Findings suggest that combination therapy using CoQ10 and creatine may be useful in treatment of neurodegenerative diseases such as PD and HD.