p(MGI:Itpkb) increases a(HBP:Astrogliosis)

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PubMed:24401760

We show here that ITPKB protein level was increased 3-fold in the cerebral cortex of most patients with Alzheimer's disease compared with control subjects, and accumulated in dystrophic neurites associated to amyloid plaques. In mouse Neuro-2a neuroblastoma cells, Itpkb overexpression was associated with increased cell apoptosis and increased β-secretase 1 activity leading to overproduction of amyloid-β peptides. In this cellular model, an inhibitor of mitogen-activated kinase kinases 1/2 completely prevented overproduction of amyloid-β peptides. Transgenic overexpression of ITPKB in mouse forebrain neurons was not sufficient to induce amyloid plaque formation or tau hyperphosphorylation. However, in the 5X familial Alzheimer's disease mouse model, neuronal ITPKB overexpression significantly increased extracellular signal-regulated kinases 1/2 activation and β-secretase 1 activity, resulting in exacerbated Alzheimer's disease pathology as shown by increased astrogliosis, amyloid-β40 peptide production and tau hyperphosphorylation.

Related Edges 18

• a(CHEBI:"amyloid-beta") positiveCorrelation p(MGI:Bace1)
• a(HBP:"SL-327") directlyDecreases p(MGI:Map2k1)
• a(HBP:"SL-327") directlyDecreases p(MGI:Map2k2)
• a(HBP:"SL-327") decreases a(CHEBI:"amyloid-beta")
• a(HBP:Astrogliosis) biomarkerFor path(MESH:"Alzheimer Disease")
• p(HGNC:APP, frag("672_711")) biomarkerFor path(MESH:"Alzheimer Disease")
• p(HGNC:ITPKB) positiveCorrelation path(MESH:"Plaque, Amyloid")
• p(HGNC:MAPT, pmod(HBP:hyperphosphorylation)) biomarkerFor path(MESH:"Alzheimer Disease")
• p(MGI:Bace1) positiveCorrelation a(CHEBI:"amyloid-beta")
• p(MGI:Itpkb) increases bp(GO:"apoptotic process")
• p(MGI:Itpkb) increases p(MGI:Bace1)
• p(MGI:Itpkb) increases act(p(MGI:Bace1))
• p(MGI:Itpkb) increases act(p(MGI:Map2k1))
• p(MGI:Itpkb) increases act(p(MGI:Map2k2))
• p(MGI:Itpkb) increases p(HGNC:APP, frag("672_711"))
• p(MGI:Itpkb) increases p(HGNC:MAPT, pmod(HBP:hyperphosphorylation))
• path(MESH:"Alzheimer Disease") increases p(HGNC:ITPKB)
• path(MESH:"Plaque, Amyloid") positiveCorrelation p(HGNC:ITPKB)

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If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.

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