act(p(HGNC:PPP1CA)) directlyDecreases p(HGNC:MAPT, pmod(HBP:hyperphosphorylation))

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PubMed:25001178

In primary neurons, overexpression of miR-125b causes tau hyperphosphorylation and an upregulation of p35, cdk5, and p44/42-MAPK signaling. In parallel, the phosphatases DUSP6 and PPP1CA and the anti-apoptotic factor Bcl-W are downregulated as direct targets of miR-125b. Knockdown of these phosphatases induces tau hyperphosphorylation, and overexpression of PPP1CA and Bcl-W prevents miR-125b-induced tau phosphorylation, suggesting that they mediate the effects of miR-125b on tau. Conversely, suppression of miR-125b in neurons by tough decoys reduces tau phosphorylation and kinase expression/activity. Injecting miR-125b into the hippocampus of mice impairs associative learning and is accompanied by downregulation of Bcl-W, DUSP6, and PPP1CA, resulting in increased tau phosphorylation in vivo. Importantly, DUSP6 and PPP1CA are also reduced in AD brains.

Related Edges 8

• act(p(HGNC:CDK5), ma(kin)) directlyIncreases p(HGNC:MAPT, pmod(HBP:hyperphosphorylation))
• m(MIRBASE:"hsa-mir-125b-1") increases act(p(HGNC:CDK5R1))
• m(MIRBASE:"hsa-mir-125b-1") increases act(p(HGNC:CDK5), ma(kin))
• m(MIRBASE:"hsa-mir-125b-1") increases act(p(HGNC:MAPK3), ma(kin))
• m(MIRBASE:"hsa-mir-125b-1") increases act(p(HGNC:MAPK1), ma(kin))
• m(MIRBASE:"hsa-mir-125b-1") directlyDecreases act(p(HGNC:PPP1CA))
• m(MIRBASE:"hsa-mir-125b-1") directlyDecreases act(p(HGNC:DUSP6))
• m(MIRBASE:"hsa-mir-125b-1") directlyDecreases act(p(HGNC:BCL2L2))

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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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