Cited by 391Genetic Neurodegenerative DiseasesCoenzyme Q10 studies and effectsNeurological diseases and metabolism

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Therapeutic Effects of Coenzyme Q10and Remacemide in Transgenic Mouse Models of Huntington's Disease

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Ferrante, Robert J., Andreassen, Ole A., Dedeoglu, Alpaslan, Ferrante, Kimberly L., Jenkins, Bruce G., Hersch, Steven M., Beal, M. Flint·2002·The Journal of Neuroscience

DOI 10.1523/jneurosci.22-05-01592.2002PMC PMC6758854

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Abstract

There is substantial evidence that bioenergetic defects and excitotoxicity may play a role in the pathogenesis of Huntington's disease (HD). Potential therapeutic strategies for neurodegenerative diseases in which there is reduced energy metabolism and NMDA-mediated excitotoxicity are the administration of the mitochondrial cofactor coenzyme Q10 and the NMDA antagonist remacemide. We found that oral administration of either coenzyme Q10 or remacemide significantly extended survival and delayed the development of motor deficits, weight loss, cerebral atrophy, and neuronal intranuclear inclusions in the R6/2 transgenic mouse model of HD. The combined treatment, using coenzyme Q10 and remacemide together, was more efficacious than either compound alone, resulting in an approximately 32 and 17% increase in survival in the R6/2 and N171-82Q mice, respectively. Magnetic resonance imaging showed that combined treatment significantly attenuated ventricular enlargement in vivo. These studies further implicate defective energy metabolism and excitotoxicity in the R6/2 and N171-82Q transgenic mouse models of HD and are of interest in comparison with the outcome of a recent clinical trial examining coenzyme Q10 and remacemide in HD patients.

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Authors: Ferrante, R. J., Andreassen, O. A., Dedeoglu, A., Ferrante, K. L., Jenkins, B. G., Hersch, S. M., & Beal, M. F.
Affiliations: Boston University (US)
NewYork–Presbyterian Hospital (US)
Harvard University (US)
ORCID: Andreassen, Ole A.
Dedeoglu, Alpaslan
Ferrante, Kimberly L.
Hersch, Steven M.
Venue: The Journal of Neuroscience
Publisher: Society for Neuroscience
Published: 2002-03-01
Volume: 22
Issue: 5
Pages: 1592-1599
ISSN: 0270-6474 (ISSN-L)
1529-2401
DOI: 10.1523/jneurosci.22-05-01592.2002
PMC: PMC6758854
OpenAlex: W1949056714
Cited by: 391
References: 50
Citations by year: 2025: 8 · 2024: 8 · 2023: 7 · 2022: 6 · 2021: 7 · 2020: 10 · 2019: 9 · 2018: 12 · 2017: 7 · 2016: 12 · 2015: 8 · 2014: 23 · 2013: 11 · 2012: 23
FWCI: 12.48
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Neuroscience (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5r29ns037102-02)
National Institute on Aging (AG 12992, AG 13846, P30AG013846, P01AG012992)
National Institute of Neurological Disorders and Stroke (NS37102, NS 35255, NS38180, R01NS035255)
National Center for Complementary and Integrative Health (AT00613, R01AT000613, U01AT000613)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Coenzyme Q10 studies and effects
Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
Keywords: Huntington's disease, coenzyme Q10, remacemide, R6/2 transgenic mice, mitochondrial bioenergetics, excitotoxicity, NMDA receptor antagonism, neuronal intranuclear inclusions, brain atrophy, ventriculomegaly, motor impairment, combination therapy, survival extension
MeSH terms: Huntingtin Protein, Acetamides, Administration, Oral, Animals, Behavior, Animal, Body Weight, Brain, Cerebral Ventricles, Coenzymes, Disease Models, Animal, Drug Evaluation, Preclinical, Drug Synergism, Female, Humans, Huntington Disease, Magnetic Resonance Imaging, Male, Mice, Transgenic, Motor Activity, Nerve Tissue Proteins, Nuclear Proteins, Organ Size, Ubiquinone, Survival Rate, Treatment Outcome, Disease Progression, Mice

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Therapeutic Effects of Coenzyme Q10and Remacemide in Transgenic Mouse Models of Huntington's Disease

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