INT61316
From wiki-pain
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Sentences Mentioned In
Key: | Protein | Mutation | Event | Anatomy | Negation | Speculation | Pain term | Disease term |
Taking advantage of barely detectable quantities of GM1 expressed in NECs (Yanagisawa et al., 2006a), we evaluated the incorporation of GM1 into the NECs by staining with Ctxb, a probe recognizing GM1 and other related gangliosides. | |||||||||||||||
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Matthews and colleagues demonstrated a 30%40% increase in cerebral cortex mitochondrial concentrations of CoQ9 and CoQ10 at 12 months in mice,2 and Smith and colleagues found brain levels of CoQ9 and CoQ10 to increase with oral supplementation in R6/2 mouse models of HD.8 Central nervous system penetration of oral CoQ10 in humans has not been studied.
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s have been reported to bind to rat phaeochromocytoma, PC12 cells; the binding does not seem to be with GM1, but rather with fucosylated GM1, which is expressed (Yanagisawa et al., 2006b). | |||||||||||||||
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Like the levels of CoQ9 and CoQ10 in serum, the levels of CoQ9 and CoQ10 in the liver and heart were significantly lowered by simvastatin administration. | |||||||||||||||
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Activation of uncoupling proteins by CoQ10 has been associated with neuroprotection against MPTP toxicity in the substantia nigra of primates.10,11,76
Clinical studies of CoQ10 effects in neurodegenerative disease | |||||||||||||||
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Induced CoQ10 deficiency in cells genetically altered to lack autophagy resulted in apoptosis, indicating that the autophagy was likely protective.25
Mitochondrial dysfunction and neurodegenerative disease: A rationale for testing CoQ10 | |||||||||||||||
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Coincident with aberrant mitochondrial function in PD, CoQ10 levels are significantly decreased in mitochondria from SN neurons and platelets in PD patients, and levels of CoQ10 have been shown to correlate with activity of complexes I and II/III.37 Decreased levels of CoQ10 in brain cortex relative to age-matched controls have also been demonstrated, though no reduction was found in the SN, cerebellum, or striatum.51 In serum, there is a reduction in the ratio of reduced to oxidized CoQ10 in PD37,52,53 and ALS.38,40 However, serum total levels are no different from controls in PD,54 HD,55 and ALS.40,56
Evidence of neuroprotective effects of coenzyme Q10 in vitro | |||||||||||||||
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Of note, this subgroup had significantly lower baseline serum CoQ10 levels.31 | |||||||||||||||
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Nine genes are presumed to be involved in CoQ10 biosynthesis, and as of now, mutations in three genes have been shown to result in primary CoQ10 deficiency: PDSS1, PDSS2, and COQ2.21 Duncan and colleagues found an autosomal recessive form of neonatal-onset primary coenzyme Q10 deficiency resulting from a nonsense mutation in COQ9.24 | |||||||||||||||
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Consequences of CoQ10 deficiency | |||||||||||||||
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Nine genes are presumed to be involved in CoQ10 biosynthesis, and as of now, mutations in three genes have been shown to result in primary CoQ10 deficiency: PDSS1, PDSS2, and COQ2.21 Duncan and colleagues found an autosomal recessive form of neonatal-onset primary coenzyme Q10 deficiency resulting from a nonsense mutation in COQ9.24 | |||||||||||||||
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With regard to FA, succinate-reduced CoQ10 has been shown to protect membrane lipids and complex II against iron injury in human heart homogenate in vitro.7 Mitochondria-targeted CoQ10, MitoQ, prevented cell death in fibroblasts of FA patients which were treated with buthionine sulfoxime (BSO), an inhibitor of glutathione biosynthesis that causes death of FA fibroblasts but not of those of controls.66
CoQ10 effects in healthy animals and animal models of neurodegenerative disease | |||||||||||||||
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Similar feeding for one month at 24 months of age resulted in 10% increases in cerebral levels.2 In this same study, in 10 animals administered 3-nitropropionic acid, striatal lesions were attenuated by 90% in the CoQ10 group relative to the placebo group.2 | |||||||||||||||
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Interestingly, CoQ10 and its analog idebenone were studied in FA using cardiac prior to neurologic outcomes. | |||||||||||||||
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Coincident with aberrant mitochondrial function in PD, CoQ10 levels are significantly decreased in mitochondria from SN neurons and platelets in PD patients, and levels of CoQ10 have been shown to correlate with activity of complexes I and II/III.37 Decreased levels of CoQ10 in brain cortex relative to age-matched controls have also been demonstrated, though no reduction was found in the SN, cerebellum, or striatum.51 In serum, there is a reduction in the ratio of reduced to oxidized CoQ10 in PD37,52,53 and ALS.38,40 However, serum total levels are no different from controls in PD,54 HD,55 and ALS.40,56
Evidence of neuroprotective effects of coenzyme Q10 in vitro | |||||||||||||||
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Induced CoQ10 deficiency in cells genetically altered to lack autophagy resulted in apoptosis, indicating that the autophagy was likely protective.25
Mitochondrial dysfunction and neurodegenerative disease: A rationale for testing CoQ10 | |||||||||||||||
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This result suggests that GM1 itself could not sequester A? | |||||||||||||||
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In AD brains, GM1 ganglioside, one of the major brain gangliosides, is considered to bind to monomeric A? | |||||||||||||||
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No change of cell number was detected in NECs cultured in the presence of either GM1 or A? | |||||||||||||||
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Certain gangliosides, including GM1, have also been reported to inhibit A? | |||||||||||||||
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General Comments
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