Nanomicellar formulation of coenzyme Q10 (Ubisol-Q10) effectively blocks ongoing neurodegeneration in the mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model: potential use as an adjuvant treatment in Parkinson's disease

Sikorska, Marianna; Lanthier, Patricia; Miller, Harvey; Beyers, Melissa; Sodja, Caroline; Zurakowski, Bogdan; Gangaraju, Sandhya; Pandey, Siyaram; Sandhu, Jagdeep K.

doi:10.1016/j.neurobiolaging.2014.03.032

Cited by 70Coenzyme Q10 studies and effectsParkinson's Disease Mechanisms and TreatmentsNanoparticle-Based Drug Delivery

Nanomicellar formulation of coenzyme Q10 (Ubisol-Q10) effectively blocks ongoing neurodegeneration in the mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model: potential use as an adjuvant treatment in Parkinson's disease

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Sikorska, Marianna, Lanthier, Patricia, Miller, Harvey, Beyers, Melissa, Sodja, Caroline, Zurakowski, Bogdan, Gangaraju, Sandhya, Pandey, Siyaram, Sandhu, Jagdeep K.·2014·Neurobiology of Aging

DOI 10.1016/j.neurobiolaging.2014.03.032PMC PMC4892899

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Abstract

Although the support for the use of antioxidants, such as coenzyme Q(10) (CoQ(10)), to treat Parkinson's disease (PD) comes from the extensive scientific evidence, the results of conducted thus far clinical trials are inconclusive. It is assumed that the efficacy of CoQ(10) is hindered by insolubility, poor bioavailability, and lack of brain penetration. We have developed a nanomicellar formulation of CoQ(10) (Ubisol-Q(10)) with improved properties, including the brain penetration, and tested its effectiveness in mouse MPTP (1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine) model with the objectives to assess its potential use as an adjuvant therapy for PD. We used a subchronic MPTP model (5-daily MPTP injections), characterized by 50% loss of dopamine neurons over a period of 28 days. Ubisol-Q(10) was delivered in drinking water. Prophylactic application of Ubisol-Q(10), started 2 weeks before the MPTP exposure, significantly offset the neurotoxicity (approximately 50% neurons died in MPTP group vs. 17% in MPTP+ Ubisol-Q(10) group by day 28). Therapeutic application of Ubisol-Q(10), given after the last MPTP injection, was equally effective. At the time of intervention on day 5 nearly 25% of dopamine neurons were already lost, but the treatment saved the remaining 25% of cells, which otherwise would have died by day 28. This was confirmed by cell counts, analyses of striatal dopamine levels, and improved animals' motor skill on a beam walk test. Similar levels of neuroprotection were obtained with 3 different Ubisol-Q(10) concentrations tested, that is, 30 mg, 6 mg, or 3 mg CoQ(10)/kg body weight/day, showing clearly that high doses of CoQ(10) were not required to deliver these effects. Furthermore, the Ubisol-Q(10) treatments brought about a robust astrocytic activation in the brain parenchyma, indicating that astroglia played an active role in this neuroprotection. Thus, we have shown for the first time that Ubisol-Q(10) was capable of halting the neurodegeneration already in progress; however, to maintain it a continuous supplementation of Ubisol-Q(10) was required. The pathologic processes initiated by MPTP resumed if supplementation was withdrawn. We suggest that in addition to brain delivery of powerful antioxidants, Ubisol-Q(10) might have also supported subcellular oxidoreductase systems allowing them to maintain a favorable cellular redox status, especially in astroglia, facilitating their role in neuroprotection. Based on this data further clinical testing of this formulation in PD patients might be justifiable.

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Coenzyme Q10 offers neuroprotection in animal models of neurodegenerative diseases such as Parkinson's disease.
“Furthermore, CoQ10 offers neuroprotection in animal models of neurodegenerative diseases (e.g. Parkinson’s) [179, 180].”
From Cognitive remission: a novel objective for the treatment of major depression? (2016) · cites this paper as [180]

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Authors: Sikorska, M., Lanthier, P., Miller, H., Beyers, M., Sodja, C., Zurakowski, B., Gangaraju, S., Pandey, S., & Sandhu, J. K.
Affiliations: National Research Council Canada (CA)
University of Windsor (CA)
Corresponding author: Sandhu, Jagdeep K.
ORCID: Gangaraju, Sandhya
Pandey, Siyaram
Sandhu, Jagdeep K.
Venue: Neurobiology of Aging
Publisher: Elsevier BV
Published: 2014-10
Volume: 35
Issue: 10
Pages: 2329-2346
ISSN: 0197-4580 (ISSN-L)
DOI: 10.1016/j.neurobiolaging.2014.03.032
PMC: PMC4892899
OpenAlex: W2115314563
Cited by: 70
References: 128
Citations by year: 2026: 3 · 2025: 3 · 2024: 4 · 2023: 8 · 2022: 4 · 2021: 6 · 2020: 14 · 2019: 6 · 2018: 6 · 2017: 3 · 2016: 7 · 2015: 4 · 2014: 2
FWCI: 2.19
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Neurobiology of Aging (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
NPARC (acceptedVersion)
Funders: Michael J Fox Foundation
National Research Council Canada
Canadian Institute for Health Research
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Coenzyme Q10 studies and effects
Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
Keywords: coenzyme Q10, Parkinson's disease, MPTP-induced neurotoxicity, neuroprotection, dopaminergic neurons, brain penetration, antioxidants, adjuvant therapy, astrocyte activation, striatal dopamine, motor function, neurodegeneration, drug delivery, bioavailability, dose-response relationship, astrocytes
MeSH terms: Animals, Antioxidants, Astrocytes, Chemistry, Pharmaceutical, Disease Models, Animal, Male, Mice, Inbred C57BL, Micelles, Oxidation-Reduction, Parkinson Disease, Ubiquinone, 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, Neuroprotective Agents, Nanoparticles, Dopaminergic Neurons

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Nanomicellar formulation of coenzyme Q10 (Ubisol-Q10) effectively blocks ongoing neurodegeneration in the mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model: potential use as an adjuvant treatment in Parkinson's disease

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