INT61316

Context Info Confidence 0.73 First Reported 1995 Last Reported 2011 Negated 6 Speculated 1 Reported most in Body Documents 59 Total Number 61 Disease Relevance 32.81 Pain Relevance 3.95

molecular_function (Coq10a) cellular_component (Coq10a) biological_process (Coq10a)

Anatomy Link Frequency brain 6 body 6 liver 3 heart 3 striatum 2 Coq10a (Mus musculus)

Pain Link Frequency Relevance Heat adenocard 21 99.24 Substantia nigra 78 99.14 Opioid 16 98.86 cerebral cortex 65 97.84 opioid receptor 6 97.84 Central nervous system 40 97.28 dorsal root ganglion 8 96.24 Inflammation 79 94.80 sodium channel 12 94.76 narcan 8 94.72

Disease Link Frequency Relevance Heat Gangliosidoses 2 100.00 Disease 1020 99.96 Neurodegenerative Disease 561 99.84 Ataxia 325 99.84 Vibrio Infection 49 99.80 Death 162 99.76 Targeted Disruption 192 99.70 Miller Fisher Syndrome 11 99.12 Parkinson's Disease 242 99.04 Neuropathy 52 98.86

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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.

Gene_expression (expressed) of GM1

1) Confidence 0.73 Published 2010 Journal ASN NEURO Section Body Doc Link PMC2838405 Disease Relevance 0.07 Pain Relevance 0

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.

Gene_expression (levels) of CoQ10 in Central nervous system associated with central nervous system, disease and cerebral cortex

2) Confidence 0.65 Published 2009 Journal Neuropsychiatric Disease and Treatment Section Body Doc Link PMC2785862 Disease Relevance 0.80 Pain Relevance 0.10

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).

Gene_expression (expressed) of GM1 associated with pheochromocytoma

3) Confidence 0.63 Published 2010 Journal ASN NEURO Section Body Doc Link PMC2838405 Disease Relevance 0.25 Pain Relevance 0

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.

Gene_expression (levels) of CoQ10 in heart

4) Confidence 0.62 Published 2007 Journal Journal of Clinical Biochemistry and Nutrition Section Body Doc Link PMC2275764 Disease Relevance 0.30 Pain Relevance 0

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

Gene_expression (effects) of CoQ10 in substantia nigra associated with parkinson's disease, toxicity, substantia nigra and neurodegenerative disease

5) Confidence 0.56 Published 2009 Journal Neuropsychiatric Disease and Treatment Section Body Doc Link PMC2785862 Disease Relevance 1.53 Pain Relevance 0.09

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

Gene_expression (testing) of CoQ10 associated with parkinson's disease, neurodegenerative disease and apoptosis

6) Confidence 0.56 Published 2009 Journal Neuropsychiatric Disease and Treatment Section Body Doc Link PMC2785862 Disease Relevance 1.11 Pain Relevance 0

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

Gene_expression (levels) of CoQ10 in striatum associated with disease and motor neuron diseases

7) Confidence 0.56 Published 2009 Journal Neuropsychiatric Disease and Treatment Section Body Doc Link PMC2785862 Disease Relevance 1.08 Pain Relevance 0

Of note, this subgroup had significantly lower baseline serum CoQ10 levels.31

Gene_expression (levels.31) of CoQ10

8) Confidence 0.56 Published 2009 Journal Neuropsychiatric Disease and Treatment Section Body Doc Link PMC2785862 Disease Relevance 0.74 Pain Relevance 0

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

Gene_expression (biosynthesis) of CoQ10

9) Confidence 0.56 Published 2009 Journal Neuropsychiatric Disease and Treatment Section Body Doc Link PMC2785862 Disease Relevance 0.95 Pain Relevance 0.06

Consequences of CoQ10 deficiency

Gene_expression (deficiency) of CoQ10

10) Confidence 0.56 Published 2009 Journal Neuropsychiatric Disease and Treatment Section Body Doc Link PMC2785862 Disease Relevance 1.00 Pain Relevance 0.09

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

Gene_expression (deficiency) of CoQ10

11) Confidence 0.56 Published 2009 Journal Neuropsychiatric Disease and Treatment Section Body Doc Link PMC2785862 Disease Relevance 0.96 Pain Relevance 0.06

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

Gene_expression (effects) of CoQ10 in fibroblasts associated with ataxia, injury, neurodegenerative disease and death

12) Confidence 0.56 Published 2009 Journal Neuropsychiatric Disease and Treatment Section Body Doc Link PMC2785862 Disease Relevance 1.39 Pain Relevance 0.06

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

Gene_expression (group) of CoQ10

13) Confidence 0.56 Published 2009 Journal Neuropsychiatric Disease and Treatment Section Body Doc Link PMC2785862 Disease Relevance 0.54 Pain Relevance 0.08

Interestingly, CoQ10 and its analog idebenone were studied in FA using cardiac prior to neurologic outcomes.

Gene_expression (studied) of CoQ10 associated with ataxia

14) Confidence 0.56 Published 2009 Journal Neuropsychiatric Disease and Treatment Section Body Doc Link PMC2785862 Disease Relevance 0.73 Pain Relevance 0

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

Gene_expression (levels) of CoQ10 in striatum associated with disease and motor neuron diseases

15) Confidence 0.56 Published 2009 Journal Neuropsychiatric Disease and Treatment Section Body Doc Link PMC2785862 Disease Relevance 1.09 Pain Relevance 0.03

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

Gene_expression (deficiency) of CoQ10 associated with parkinson's disease, neurodegenerative disease and apoptosis

16) Confidence 0.56 Published 2009 Journal Neuropsychiatric Disease and Treatment Section Body Doc Link PMC2785862 Disease Relevance 0.76 Pain Relevance 0

This result suggests that GM1 itself could not sequester A?

Gene_expression (itself) of GM1

17) Confidence 0.55 Published 2010 Journal ASN NEURO Section Body Doc Link PMC2838405 Disease Relevance 0.07 Pain Relevance 0

In AD brains, GM1 ganglioside, one of the major brain gangliosides, is considered to bind to monomeric A?

Gene_expression (ganglioside) of GM1 in brains

18) Confidence 0.55 Published 2010 Journal ASN NEURO Section Body Doc Link PMC2838405 Disease Relevance 0.46 Pain Relevance 0.06

No change of cell number was detected in NECs cultured in the presence of either GM1 or A?

Gene_expression (presence) of GM1

19) Confidence 0.55 Published 2010 Journal ASN NEURO Section Abstract Doc Link PMC2838405 Disease Relevance 0.52 Pain Relevance 0

Certain gangliosides, including GM1, have also been reported to inhibit A?

Gene_expression (gangliosides) of GM1

20) Confidence 0.55 Published 2010 Journal ASN NEURO Section Body Doc Link PMC2838405 Disease Relevance 0.41 Pain Relevance 0.09

General Comments

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