Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Coenzyme Q10 (CoQ10) is a powerful antioxidant that buffers the potential adverse consequences of free radicals produced during oxidative phosphorylation in the inner mitochondrial membrane. Oxidative stress, resulting in glutathione loss and oxidative DNA and protein damage, has been implicated in many neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, and Huntington's disease. Experimental studies in animal models suggest that CoQ10 may protect against neuronal damage that is produced by ischemia, atherosclerosis and toxic injury. Though most have tended to be pilot studies, there are published preliminary clinical trials showing that CoQ10 may offer promise in many brain disorders. For example, a 16-month randomized, placebo-controlled pilot trial in 80 subjects with mild Parkinson's disease found significant benefits for oral CoQ10 1,200 mg/day to slow functional deterioration. However, to date, there are no published clinical trials of CoQ10 in Alzheimer's disease. Available data suggests that oral CoQ10 seems to be relatively safe and tolerated across the range of 300-2,400 mg/day. Randomized controlled trials are warranted to confirm CoQ10's safety and promise as a clinically effective neuroprotectant.
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PMID:Coenzyme Q10: a review of its promise as a neuroprotectant. 1719 65

The evidence supporting a treatment benefit for coenzyme Q10 (CoQ10) in primary mitochondrial disease (mitochondrial disease) whilst positive is limited. Mitochondrial disease in this context is defined as genetic disease causing an impairment in mitochondrial oxidative phosphorylation (OXPHOS). There are no treatment trials achieving the highest Level I evidence designation. Reasons for this include the relative rarity of mitochondrial disease, the heterogeneity of mitochondrial disease, the natural cofactor status and easy 'over the counter availability' of CoQ10 all of which make funding for the necessary large blinded clinical trials unlikely. At this time the best evidence for efficacy comes from controlled trials in common cardiovascular and neurodegenerative diseases with mitochondrial and OXPHOS dysfunction the etiology of which is most likely multifactorial with environmental factors playing on a background of genetic predisposition. There remain questions about dosing, bioavailability, tissue penetration and intracellular distribution of orally administered CoQ10, a compound which is endogenously produced within the mitochondria of all cells. In some mitochondrial diseases and other commoner disorders such as cardiac disease and Parkinson's disease low mitochondrial or tissue levels of CoQ10 have been demonstrated providing an obvious rationale for supplementation. This paper discusses the current state of the evidence supporting the use of CoQ10 in mitochondrial disease.
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PMID:The evidence basis for coenzyme Q therapy in oxidative phosphorylation disease. 1748 45

Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive loss of dopaminergic neurons within the substantia nigra pars compacta. Experimental and clinical data point to a defect of the mitochondrial respiratory chain as a major pathogenetic factor in PD. Although the restoration of mitochondrial respiration and reduction of oxidative stress by coenzyme Q(10) (CoQ10) could induce neuroprotective effects against the dopaminergic cell death in PD, these effects of CoQ10 could also improve the dopaminergic dysfunction. Thus CoQ10 might theoretically exert both neuroprotective and symptomatic effects in PD. Current data from controlled clinical trials are not sufficient to answer conclusively whether CoQ10 is neuroprotective in PD. Moreover, several open and controlled pilot studies on symptomatic effects of CoQ10 revealed inconsistent results. A recent randomized, double-blind, placebo-controlled trial showed no symptomatic effects in PD. CoQ10 is well tolerated and safe as both monotherapy and add-on medication in PD patients. The present review discusses the current knowledge on neuroprotective and symptomatic actions of CoQ10 in PD.
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PMID:[Coenzyme Q10 in Parkinson's disease. Symptomatic or neuroprotective effects?]. 1750 94

MitoQ is an orally active antioxidant that has the ability to target mitochondrial dysfunction. The agent is currently under development by Antipodean Pharmaceuticals Inc in phase II clinical trials for Parkinson's disease and liver damage associated with HCV infection. MitoQ has demonstrated encouraging preclinical results in numerous studies in isolated mitochondria, cells and tissues undergoing oxidative stress and apoptotic death. MitoQ aims to not only mimic the role of the endogenous mitochondrial antioxidant coenzyme Q10 (CoQ10), but also to augment substantially the antioxidant capacity of CoQ to supraphysiological levels in a mitochondrial membrane potential-dependent manner. MitoQ represents the first foray into the clinic in an attempt to deliver an antioxidant to an intracellular region that is responsible for the formation of increased levels of potentially deleterious reactive oxygen species. Results from the clinical trials with MitoQ will have important repercussions on the relevance of a mitochondrial-targeted approach.
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PMID:MitoQ--a mitochondria-targeted antioxidant. 1764 4

Coenzyme Q10 (CoQ10) is a promising agent for neuroprotection in neurodegenerative diseases. We tested the effects of various doses of two formulations of CoQ10 in food and found that administration in the diet resulted in significant protection against loss of dopamine (DA), which was accompanied by a marked increase in plasma concentrations of CoQ10. We further investigated the neuroprotective effects of CoQ10, reduced CoQ10 (ubiquinol), and CoQ10 emulsions in the (MPTP) model of Parkinson's disease (PD). We found neuroprotection against MPTP induced loss of DA using both CoQ10, and reduced CoQ10, which produced the largest increases in plasma concentrations. Lastly, we administered CoQ10 in the diet to test its effects in a chronic MPTP model induced by administration of MPTP by Alzet pump for 1 month. We found neuroprotective effects against DA depletion, loss of tyrosine hydroxylase neurons and induction of alpha-synuclein inclusions in the substantia nigra pars compacta. The finding that CoQ10 is effective in a chronic dosing model of MPTP toxicity, is of particular interest, as this may be more relevant to PD. These results provide further evidence that administration of CoQ10 is a promising therapeutic strategy for the treatment of PD.
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PMID:Therapeutic effects of coenzyme Q10 (CoQ10) and reduced CoQ10 in the MPTP model of Parkinsonism. 1797 81

Coenzyme Q10, an endogenous lipophilic antioxidant, plays an indispensable role in ATP synthesis. The therapeutic value of coenzyme Q10 in Parkinson's disease and other neurodegenerative disorders is still being tested and the preliminary results are promising. The 1-methyl-4-phenyl-1, 2, 3, 6 tetrahydropyridine (MPTP)-treated mouse is a valid and accepted animal model for Parkinson's disease. 1-methyl-4-phenylpyridinium (MPP(+)) is an active toxic metabolite of MPTP. MPP(+) and MPTP are known to induce oxidative stress and mitochondrial dysfunction. However, the effect of MPP(+) and MPTP on coenzyme Q is not clearly understood. The present study investigated the in vitro and in vivo effect of MPP(+) and MPTP on coenzyme Q content. Coenzyme Q content was measured using HPLC-UV detection methods. In the in vitro studies, MPP(+) (0-50 microM) was incubated with SH-SY5Y human neuroblastoma cells and NG-108-15 (mouse/rat, neuroblastomaxglioma hybrid) cells. MPP(+) concentration dependently increased coenzyme Q10 content in SH-SY5Y cells. In NG-108-15 cells, MPP(+) concentration dependently increased both coenzyme Q9 and Q10 content. In the in vivo study, mice were administered with MPTP (30 mg/kg, twice 16 h apart) and sacrificed one week after the last administration. Administration of MPTP to mice significantly increased coenzyme Q9 and coenzyme Q10 levels in the nigrostriatal tract. However, MPTP did not affect the coenzyme Q content in the cerebellum, cortex and pons. This study demonstrated that MPP(+)/MPTP significantly affected the coenzyme Q content in the SH-SY5Y and NG-108 cells and in the mouse nigrostriatal tract.
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PMID:Effect of dopaminergic neurotoxin MPTP/MPP+ on coenzyme Q content. 1856 46

Parkinson disease (PD) is associated with progressive loss of dopaminergic neurons in the substantia nigra, as well as with more-widespread neuronal changes that cause complex and variable motor and nonmotor symptoms. Recent rapid advances in PD genetics have revealed a prominent role for mitochondrial dysfunction in the pathogenesis of the disease, and the products of several PD-associated genes, including SNCA, Parkin, PINK1, DJ-1, LRRK2 and HTR2A, show a degree of localization to the mitochondria under certain conditions. Impaired mitochondrial function is likely to increase oxidative stress and might render cells more vulnerable to this and other related processes, including excitotoxicity. The mitochondria, therefore, represent a highly promising target for the development of disease biomarkers by use of genetic, biochemical and bioimaging approaches. Novel therapeutic interventions that modify mitochondrial function are currently under development, and a large phase III clinical trial is underway to examine whether high-dose oral coenzyme Q10 will slow disease progression. In this Review, we examine evidence for the roles of mitochondrial dysfunction and increased oxidative stress in the neuronal loss that leads to PD and discuss how this knowledge might further improve patient management and aid in the development of 'mitochondrial therapy' for PD.
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PMID:Mitochondrial biology and oxidative stress in Parkinson disease pathogenesis. 1897

Parkinson's disease (PD) is the second most common neurodegenerative disorder, after Alzheimer's disease. In PD, motor symptoms result from the degeneration and loss of pigmented dopaminergic neurons of the substantia nigra pars compacta of the basal ganglia. Other neuronal fields and neurotransmitter systems are also involved, including non-adrenergic, serotonergic and cholinergic neurons. Since the early 1960s the treatment of PD has been based on the pharmacologic replacement of dopamine accomplished with the precursor of dopamine, 3, 4-dihydroxy-L-phenylalanine (L-dopa). The addition of carbidopa, an inhibitor of the decarboxylase represented a tremendous improvement in therapy and is still a mainstay of the treatment of PD. Dopamine agonists may also be used, as well as inhibitors of monoamine oxidase-B or catechol-O-methyltransferase. Other medications include anticholinergics and amantadine. These therapies are only symptomatic and none halt or lessen dopaminergic neuron degeneration and the progression of the disease. This has prompted the search for novel and alternative pharmacological targets and neuroprotective therapies. In this context, there are data to suggest a benefit from glial cell line-derived neurotrophic factor, neuroimmumophilin ligands, minocycline, Coenzyme Q10, creatine, reduced glutathione, adenosine A2A receptor antagonists as well as glutamate release inhibitors. Restorative techniques to compensate for cell loss include tissue transplantation and gene transfer therapy. Due to the paucity of data regarding non-pharmacological approaches such as diet therapy or antioxidant therapy, these await more studies. There are also few studies on medicinal plants. Other areas of increasing importance would thus include the investigation of active constituents of plants and phytomedicines with a view to the discovery of new compounds. Finally, stem cell therapy may offer the promise of restoring functionality.
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PMID:Drugs used to treat Parkinson's disease, present status and future directions. 1899 61

A large body of evidence from postmortem brain tissue and genetic analysis in humans and biochemical and pathological studies in animal models (transgenic and toxin) of neurodegeneration suggest that mitochondrial dysfunction is a common pathological mechanism. Mitochondrial dysfunction from oxidative stress, mitochondrial DNA deletions, pathological mutations, altered mitochondrial morphology, and interaction of pathogenic proteins with mitochondria leads to neuronal demise. Therefore, therapeutic approaches targeting mitochondrial dysfunction and oxidative damage hold great promise in neurodegenerative diseases. This review discusses the potential therapeutic efficacy of creatine, coenzyme Q10, idebenone, synthetic triterpenoids, and mitochondrial targeted antioxidants (MitoQ) and peptides (SS-31) in in vitro studies and in animal models of Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and Alzheimer's disease. We have also reviewed the current status of clinical trials of creatine, coenzyme Q10, idebenone, and MitoQ in neurodegenerative disorders. Further, we discuss newly identified therapeutic targets, including peroxisome proliferator-activated receptor-gamma-coactivator and sirtuins, which provide promise for future therapeutic developments in neurodegenerative disorders.
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PMID:Mitochondrial approaches for neuroprotection. 1907 59

Coenzyme Q10 (CoQ10) is known to be highly hydrophobic and, as such, insoluble in water: this leads to serious inconvenience when trying to incorporate it in food products. Its absorption is also known to be very limited. PureSorb-Q40 (P40) (Water-soluble type CoQ10 powder, CoQ10 content 40 w/w % was developed in order to improve its use with food products and to enhance its absorption. In the present study the absorption of this novel formulation was compared to a conventional lipid soluble CoQ10 by administering both products to rats and humans. Acute, single-administration studies in rats showed that P40 has a higher absorption, compared to lipid soluble CoQ10, both in prandial and fasting states. Similarly, single administration in humans revealed a higher absorption level for P40, taken in the fasting state or together with meals. In the rat study, no adverse effects were observed with P40 at doses up to 2,000 mg/kg in both sexes. In a double-blind, placebo controlled, comparative study conducted on 46 healthy volunteers and randomly divided into two groups, in the group receiving 900~mg of CoQ10 per day, for 4 consecutive weeks, the average level at two weeks was 8.79 +/- 3.34 microg/mL, similar to the corresponding level after 4 weeks (8.33 +/- 4.04 microg/mL). After 2 weeks of washout, serum CoQ10 level decreased to 1.30 +/- 0.49 microg/mL. P40 intake did not cause any significant changes in symptoms and clinical laboratory tests as assessed by physical, hematological, blood biochemical or urinalysis. Clinical examinations also did not reveal any abnormalities. The above blood (serum) CoQ10 level at 2 weeks after start of intake was compared with other reported values. The same dose of CoQ10 (900mg/day), when administered by softgel capsules yielded a plasma CoQ10 concentration of 3.6 microg/mL, while P40 levels were 8.79 +/- 3.34 microg/mL. These levels are remarkably high for instance when compared to the corresponding levels obtained, in patients affected by Parkinson's disease, with CoQ10 doses up to 2,400mg/day. A clinical study was conducted using doses of 300 mg/day and 600 mg/day, in patients affected by cardiovascular disease. Also in this case there was linearity in the response with the levels obtained by administering P40 at a dose of 100 and 900 mg/day.
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PMID:Blood CoQ10 levels and safety profile after single-dose or chronic administration of PureSorb-Q40: animal and human studies. 1909 18


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