Cited by 114Genetic Neurodegenerative DiseasesCoenzyme Q10 studies and effectsParkinson's Disease Mechanisms and Treatments

Combination therapy using minocycline and coenzyme Q10 in R6/2 transgenic Huntington's disease mice

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Stack, Edward C., Smith, Karen M., Ryu, Hoon, Cormier, Kerry, Chen, Minghua, Hagerty, Sean W., Del Signore, Steven J., Cudkowicz, Merit E. +2 more·2006·Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease

Abstract

Huntington's disease (HD) is a fatal neurodegenerative disorder of genetic origin with no known therapeutic intervention that can slow or halt disease progression. Transgenic murine models of HD have significantly improved the ability to assess potential therapeutic strategies. The R6/2 murine model of HD, which recapitulates many aspects of human HD, has been used extensively in pre-clinical HD therapeutic treatment trials. Of several potential therapeutic candidates, both minocycline and coenzyme Q10 (CoQ10) have been demonstrated to provide significant improvement in the R6/2 mouse. Given the specific cellular targets of each compound, and the broad array of abnormalities thought to underlie HD, we sought to assess the effects of combined minocycline and CoQ10 treatment in the R6/2 mouse. Combined minocycline and CoQ10 therapy provided an enhanced beneficial effect, ameliorating behavioral and neuropathological alterations in the R6/2 mouse. Minocycline and CoQ10 treatment significantly extended survival and improved rotarod performance to a greater degree than either minocycline or CoQ10 alone. In addition, combined minocycline and CoQ10 treatment attenuated gross brain atrophy, striatal neuron atrophy, and huntingtin aggregation in the R6/2 mice relative to individual treatment. These data suggest that combined minocycline and CoQ10 treatment may offer therapeutic benefit to patients suffering from HD.

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  • Combination therapy of CoQ10 and minocycline in the R6/2 HD mouse model resulted in significantly increased amelioration of behavioral and neuropathological deficits, extended survival, improved rotarod performance and attenuated striatal neuron atrophy, as compared to either minocycline or CoQ10 alone.

    “The combination therapy of CoQ10 and minocycline in R6/2 transgenic mouse model of HD resulted in a significantly increased amelioration of behavioral and neuropathological deficits, extended survival, improved rotarod performance and attenuated striatal neuron atrophy, as compared to either minocycline or CoQ10 alone153.”

    From Mitochondrial Approaches for Neuroprotection (2008) · cites this paper as [153]

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  1. R.T. Matthews, L. Yang, S. Browne, M. Baik, M.F. Beal, Coenzyme Q10 administration increases brain mitochondrial concentrations and exerts neuroprotective effects, Proc. Natl. Acad. Sci. U. S. A. 95 (1998) 8892 -8897.

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Authors
Stack, E. C., Smith, K. M., Ryu, H., Cormier, K., Chen, M., Hagerty, S. W., Del Signore, S. J., Cudkowicz, M. E., Friedlander, R. M., & Ferrante, R. J.
Affiliations
  • Boston University (US)
  • Edith Nourse Rogers Memorial Veterans Hospital (US)
  • Brigham and Women's Hospital (US)
  • Harvard University (US)
Corresponding author
Ferrante, Robert J.
Venue
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
Publisher
Elsevier BV
Published
2006-03
Volume
1762
Issue
3
Pages
373-380
ISSN
0925-4439 (ISSN-L)
OpenAlex
W2124661414
Cited by
114
References
40
Citations by year
2026: 1 · 2024: 5 · 2023: 3 · 2022: 3 · 2021: 5 · 2020: 4 · 2019: 5 · 2018: 2 · 2017: 1 · 2016: 4 · 2015: 3 · 2014: 9 · 2013: 4 · 2012: 7
FWCI
3.01
Type
journal article
Language
en
Open access
Locations
  • Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Ministerio de Economía y Competitividad
  • National Institutes of Health
  • National Institute of Neurological Disorders and Stroke (R01NS039324, U01NS045806, NS 045242, P01NS045242, NS045806, NS039324)
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
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
Keywords
Huntington's disease, minocycline, coenzyme Q10, combination therapy, R6/2 transgenic mice, neuroprotection, huntingtin aggregation, brain atrophy, rotarod performance, survival, neurodegeneration
MeSH terms
Huntingtin Protein, Animals, Anti-Bacterial Agents, Behavior, Animal, Body Weight, Coenzymes, Disease Models, Animal, Drug Therapy, Combination, Humans, Huntington Disease, Mice, Transgenic, Minocycline, Nerve Tissue Proteins, Nuclear Proteins, Ubiquinone, Survival Rate, Microglia, Cytoprotection, Mice

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