INT307464

Context Info Confidence 0.12 First Reported 2010 Last Reported 2010 Negated 0 Speculated 0 Reported most in Body Documents 1 Total Number 7 Disease Relevance 0.42 Pain Relevance 0.43

cytosol (Gsk3a) signal transduction (Gsk3a) carbohydrate metabolic process (Gsk3a)

Anatomy Link Frequency neurons 4 Gsk3a (Rattus norvegicus)

Pain Link Frequency Relevance Heat agonist 49 100.00 nMDA receptor 21 99.98 Glutamate 35 92.88 antagonist 28 79.52 addiction 14 73.88 withdrawal 14 5.00 Spinal cord 7 5.00 Inflammation 7 5.00 Pain 7 5.00

Disease Link Frequency Relevance Heat Apoptosis 91 85.52 Death 42 31.20 Pain 7 5.00 Neurodegenerative Disease 7 5.00 INFLAMMATION 7 5.00

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

In a previous work, the effect of several nucleotidic agonists on GSK3 phosphorylation was investigated, and among them, BzATP resulted to be the most potent, through the activation of the P2X7 nucleotide receptor.

Regulation (effect) of Phosphorylation (phosphorylation) of GSK3 associated with agonist

1) Confidence 0.12 Published 2010 Journal Cell Mol Life Sci Section Body Doc Link PMC2858808 Disease Relevance 0 Pain Relevance 0.12

The different approaches used revealed that calcium-dependent PKC isoforms were responsible for the GSK3 phosphorylation and the neuroprotective effects displayed by the three effectors, which could corresponded to PKC?

Regulation (responsible) of Phosphorylation (phosphorylation) of GSK3

2) Confidence 0.12 Published 2010 Journal Cell Mol Life Sci Section Body Doc Link PMC2858808 Disease Relevance 0.13 Pain Relevance 0.05

From the present results it is clear that the full effect of NMDA-receptor activation on GSK3 phosphorylation is obtained primarily through a PKC-dependent pathway, in the same way that BzATP acting through P2X7 receptors.

Regulation (effect) of Phosphorylation (phosphorylation) of GSK3

3) Confidence 0.12 Published 2010 Journal Cell Mol Life Sci Section Body Doc Link PMC2858808 Disease Relevance 0.15 Pain Relevance 0.05

Recent studies have further investigated the intracellular signalling mechanisms triggered by nucleotide receptors and have demonstrated the coupling of P2Y13 and P2X7 receptors to GSK3 phosphorylation in rat cerebellar granule neurons.

Regulation (coupling) of Phosphorylation (phosphorylation) of GSK3 in neurons

4) Confidence 0.09 Published 2010 Journal Cell Mol Life Sci Section Body Doc Link PMC2858808 Disease Relevance 0 Pain Relevance 0.05

P2X7 and NMDA receptors converge on GSK3 phosphorylation in granule neurons

Regulation (converge) of Phosphorylation (phosphorylation) of GSK3 in neurons associated with nmda receptor

5) Confidence 0.09 Published 2010 Journal Cell Mol Life Sci Section Body Doc Link PMC2858808 Disease Relevance 0 Pain Relevance 0.16

In addition, MAPKs were also involved in the survival signalling mechanism triggered by BDNF (Fig. 6).Fig. 5Effect of PKC and MAPK inhibition on GSK3 phosphorylation levels under conditions of PI3K inhibition.

Regulation (under) of Phosphorylation (phosphorylation) of GSK3

6) Confidence 0.05 Published 2010 Journal Cell Mol Life Sci Section Body Doc Link PMC2858808 Disease Relevance 0.06 Pain Relevance 0

Figure 5 show that pre-treatment with the PKC inhibitor Gö 6976 did not alter the loss in GSK3 phosphorylation levels induced by the PI3K inhibitor, but totally prevented the recovery mediated by BzATP, NMDA and BDNF.

Regulation (alter) of Phosphorylation (phosphorylation) of GSK3

7) Confidence 0.05 Published 2010 Journal Cell Mol Life Sci Section Body Doc Link PMC2858808 Disease Relevance 0.08 Pain Relevance 0

General Comments

This test has worked.