Electron transfer mediators and other metabolites and cofactors in the treatment of mitochondrial dysfunction

Orsucci, Daniele; Filosto, Massimiliano; Siciliano, Gabriele; Mancuso, Michelangelo

doi:10.1111/j.1753-4887.2009.00221.x

Cited by 16 publications

(13 citation statements)

References 72 publications

(123 reference statements)

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“…It has been used as an important supplement in a variety of chronic illnesses and age-related conditions [42][43][44]. Here CoQ10 was used to improve energy transduction and combat oxidative stress [42,45].…”

Section: Discussionmentioning

confidence: 99%

Lipid Replacement Therapy with a Glycophospholipid Formulation with NADH and CoQ10 Significantly Reduces Fatigue in Intractable Chronic Fatiguing Illnesses and Chronic Lyme Disease Patients

Nicolson¹,

Settineri²,

Ellithorpe³

2012

IJCM

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Objectives:A preliminary open label study was initiated to determine if a combination oral supplement containing a mixture of phosphoglycolipids, coenzyme Q10 and microencapsulated NADH could affect fatigue levels in long-term patients with intractable fatigue. Fatigue was determined by the validated Piper Fatigue Scale before, during and after the trial. Participants included 58 patients (30 females and 28 males) with chronic fatigue syndrome/myalgic encephalomyelitis, chronic Lyme disease or other fatiguing illnesses, such as fibromyalgia syndrome or Gulf War illness. These patients had been symptomatic for an average of 17.1 ± 0.6 years, had been seen by many physicians (15.2 ± 0.7) and had used many other supplements and drugs (35.4 ± 2.7) without apparent reductions in their fatigue. Results: Participants in the study responded to the combination test supplement, showing a 30.7% reduction in overall fatigue within 60 days (P < 0.001). Analysis of subcategories of fatigue indicated that there were significant improvements in the ability to complete tasks and activities as well as significant improvements in mood and cognitive abilities. Regression analysis of the data indicated that reductions in fatigue were gradual, consistent, and occurred with a high degree of confidence (R 2 = 0.960). The data also suggested that further reductions were likely if the participants had continued the supplement beyond the 8-week trial. Males responded slightly better to the combination supplement than females, and the patients with the most severe forms of fatigue responded slightly better than those with milder fatigue, independent of their diagnosis. Conclusions: The combination supplement was a safe and effective method to significantly reduce fatigue in long-term patients with intractable chronic fatigue.

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Section: Discussionmentioning

confidence: 99%

Lipid Replacement Therapy with a Glycophospholipid Formulation with NADH and CoQ10 Significantly Reduces Fatigue in Intractable Chronic Fatiguing Illnesses and Chronic Lyme Disease Patients

Nicolson¹,

Settineri²,

Ellithorpe³

2012

IJCM

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“…Genetic mutations linked to these diseases have been shown to disrupt the electron transport chain (ETC) (2), a mitochondrial pathway that accounts for the majority of cellular energy production (3). Chemical inhibitors of the ETC can also produce symptoms reminiscent of neurodegenerative diseases (4).…”

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confidence: 99%

Coenzyme Q protects Caenorhabditis elegans GABA neurons from calcium-dependent degeneration

Earls

Hacker²,

Watson³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Mitochondria are key regulators of cell viability and provide essential functions that protect against neurodegenerative disease. To develop a model for mitochondrial-dependent neurodegeneration in Caenorhabditis elegans, we used RNA interference (RNAi) and genetic ablation to knock down expression of enzymes in the Coenzyme Q (CoQ) biosynthetic pathway. CoQ is a required component of the ATP-producing electron transport chain in mitochondria. We found that reduced levels of CoQ result in a progressive uncoordinated (Unc) phenotype that is correlated with the appearance of degenerating GABA neurons. Both the Unc and degenerative phenotypes emerge during late larval development and progress in adults. Neuron classes in motor and sensory circuits that use other neurotransmitters (dopamine, acetylcholine, glutamate, serotonin) and body muscle cells were less sensitive to CoQ depletion. Our results indicate that the mechanism of GABA neuron degeneration is calcium-dependent and requires activation of the apoptotic gene, ced-4 (Apaf-1). A molecular cascade involving mitochondrial-initiated cell death is also consistent with our finding that GABA neuron degeneration requires the mitochondrial fission gene, drp-1. We conclude that the cell selectivity and developmental progression of CoQ deficiency in C. elegans indicate that this model may be useful for delineating the role of mitochondrial dysfunction in neurodegenerative disease.cell death | disease | mitochondria | neurodegeneration | necrosis

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“…Lack of CoQ10 in mitochondria disrupts the electron flow from complexes I and II to complex III and, consequently, leads to reduced ATP synthesis [5,6].…”

Section: ) Antioxidantsmentioning

confidence: 99%

“…A growing body of evidence indicates that oxidative stress, which is increased in damaged mitochondria, is an early event in neurodegeneration [2,[4][5][6]. Particularly, Parkinson's disease, Alzheimer's disease and Amyotrophic Lateral Sclerosis have been associated with mitochondrial alterations and, in some cases, with mutations in nuclear genes involved in mitochondrial functions [7,8].…”

Section: Introductionmentioning

confidence: 98%

Current Options in the Treatment of Mitochondrial Diseases

Scarpelli¹,

Cotelli²,

Mancuso³

et al. 2010

RPCN

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Mitochondrial diseases (MD) are disorders caused by an impairment of the mitochondrial respiratory chain function. They are usually progressive, isolated or multi-system diseases and have variable times of onset. Because mitochondria have their own DNA (mtDNA), MD can be caused by mutations in both mtDNA and nuclear DNA (nDNA). The complexity of genetic control of mitochondrial function is in part responsible for the intra- and inter-familiar clinical heterogeneity of this class of diseases. Despite the remarkable progress in understanding of the molecular bases of these disorders, therapy of MD is quite inadequate. Present options of treatment mainly include physical, pharmacological and gene therapy approaches. Aerobic exercise and physical therapy is useful to prevent or correct deconditioning and may improve exercise tolerance. Pharmacological approach is based on removing noxious metabolites, using reactive oxygen species scavengers and administrating vitamins and cofactors which is especially important in case of primary deficiencies of specific compounds such as Coenzyme Q10. Gene therapy is fascinating but it is difficult to apply because of polyplasmy and heteroplasmy. Experimental methods include gene shifting, allotopic expression, mitochondrial transfection or correcting mtDNA mutations with specific restriction endonucleases. Here, we discussed some recent patents. Progresses in each of these fields may open interesting perspectives for the future.

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Electron transfer mediators and other metabolites and cofactors in the treatment of mitochondrial dysfunction

Cited by 16 publications

References 72 publications

Lipid Replacement Therapy with a Glycophospholipid Formulation with NADH and CoQ10 Significantly Reduces Fatigue in Intractable Chronic Fatiguing Illnesses and Chronic Lyme Disease Patients

Lipid Replacement Therapy with a Glycophospholipid Formulation with NADH and CoQ10 Significantly Reduces Fatigue in Intractable Chronic Fatiguing Illnesses and Chronic Lyme Disease Patients

Coenzyme Q protects Caenorhabditis elegans GABA neurons from calcium-dependent degeneration

Current Options in the Treatment of Mitochondrial Diseases

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