composite(a(CHEBI:"amyloid-beta"), p(HGNC:CHRNA7))

Components

• a(CHEBI:"amyloid-beta")
• p(HGNC:CHRNA7)

Paradoxically, Abeta also activates the MAPK pathway through an alpha7-dependent pathway (Dineley et al., 2001; Bell et al., 2004). In human oral keratinocytes, the Ras/Raf/mitogen-activated protein kinase kinase 1/ERK pathway cooperates with the nicotine activation of the JAK/STAT-3 pathway (Arredondo et al., 2006); the Ras pathway induces STAT-3 upregulation whereas the JAK/STAT-3 pathway phosphorylates STAT-3. PubMed:19293145

Stevens et al. (2003) showed that calcineurin is involved in nicotine neuroprotection. Abeta, through alpha7 nAChRs, increases Ca2+, which phosphorylates NMDARs via calcineurin and protein tyrosine phosphatase, nonreceptor type 5 (striatum-enriched) (Snyder et al., 2005). PubMed:19293145

Abeta initiates intracellular signaling cascades via nAChRs (Fig. 3), including the MAPK kinase signaling pathway, resulting in cell death. In hippocampal slices, Abeta activates ERK-2 isoforms of the ERK MAPK. This is blocked by alpha7 antagonists, suggesting that Abeta evokes the cascade through alpha7 nAChRs (Dineley et al., 2001). PubMed:19293145

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. PubMed:19293145

Perfusion of soluble Abeta into mouse prefrontal cortex increases dopamine secretion through a mechanism that is blocked by alpha7 antagonists (Wu et al., 2007). PubMed:19293145