Evidences a(CHEBI:nicotine) to p(FPLX:PI3K)

An ever-growing body of evidence indicates that in CNS and parasympathetic nervous system neurons and in heterologous systems expressing specific nAChR subtypes, nicotine stimulates several Ca2+-dependent kinases, including PI3K, protein kinase C (PKC), protein kinase A (PKA), calmodulin-dependent protein kinase II (CAM kinase II), and extracellular signal-regulated kinases (ERKs; Refs. 108, 112, 146, 318, 469).

For instance, over-expressing PI3K in Drosophila melanogaster neurons in situ results in an increase in functional synapses as well as synaptic sprouting (Martín-Pen˜ a et al., 2006). Thus it is possible that nicotine’s activation of the PI3K pathway results in increased synaptic stability, and it would be of interest to explore this further in vertebrates. Thus, the evidence suggests that activation of nAChRs activates the PI3K/AKT pathway to favor antiapoptotic pathways and possibly induce synaptogenesis.

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).

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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.