The neuroprotective effects of nicotine are blocked by inhibitors of either PI3K or SRC family kinases, and nicotine evokes an increase in levels of phosphorylated AKT, B-cell chronic lymphocytic leukemia/lymphoma (BCL2), and BCL-2-like protein (Shimohama and Kihara, 2001), which are further downstream in the PI3K/AKT pathway (Fig. 3).
In neuroblastoma cells, as well as cultured hippocampal neurons, Abeta activates JNK and ERK, and blocking these prevents Abeta hyperphosphorylating tau protein, as does alpha7 antisense oligonucleotides or alpha7 antagonists, suggesting that Abeta may trigger tau protein phosphorylation through ERK and JNK via alpha7 receptors (Wang et al., 2003b). Abeta leads to phosphorylation of AKT in cultured mouse neurons through a mechanism that requires alpha7 nAChRs (Abbott et al., 2008), AKT phosphorylation levels returning to baseline upon prolonged application of Abeta.
In this system enhancement of Akt phosphorylation and activation of ERK pathway was observed following alpha7 agonist treatment, suggesting that Abeta inhibits the neuroprotective effect of alpha7 nAChR activation (Zhi et al., 2014)
The binding between ErbB4 and PI3K activates this latter kinase, which in turn can phosphorylate and activate its downstream target Akt
Akt phosphorylation mediates the downstream activation of an antiapoptotic pathway, which is also activated by nicotine treatment (Kihara et al., 2001)
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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.