p(RGD:Chrna7)

Entity

Name

Chrna7

Namespace

rgd

Namespace Version

20181021

Namespace URL

https://raw.githubusercontent.com/pharmacome/terminology/f2f993e599694ab5ce989cc39d789a499f75db99/external/rgd-names.belns

Intracerebral injection of Abeta into rats resulted in a loss of alpha4 and alpha7 subunits as measured by Western blotting but an increase in alpha7 mRNA (Liu et al., 2008), again suggesting that Abeta directly reduces expression of alpha7 nAChRs through mechanisms other than reduced mRNAproduction, although caution should be exercised in interpreting quantitative data from Western blot studies. It is noteworthy that a combined patch-clamp and in situ hybridization study of dissociated human brain tissue (obtained as route-of-access tissue removed during surgery) indicated that neurons near Abeta plaques retained alpha4 and alpha7 mRNA transcripts, whereas these transcripts were absent in neurons burdened with hyperphosphorylated tau protein (Wevers et al., 1999). PubMed:19293145

Calcium signaling pathways are involved both in the toxic action of Abeta and in the protection against that toxicity offered by nicotinic ligands. Given that alpha7 homomeric nAChRs are much more permeable to calcium ions than are most other nAChRs (Bertrand et al., 1993), it is to be expected that nicotinic neuroprotection mediated by nAChRs, notably alpha7, would depend upon the activation of calcium signaling pathways. ABT-418 is a nicotinic agonist that protects primary rat cortical neurons from glutamate toxicity through its activation of alpha7 nAChRs, and this is blocked when calcium is removed from the extracellular medium (Donnelly-Roberts et al., 1996). PubMed:19293145

Shortterm nicotine application also induces phosphorylation of p44/42MAPK, p38MAPK, and STAT-3 and was mediated mostly by alpha7 nAChRs in rat vascular smooth muscle cells (Wada et al., 2007). It is noteworthy that the JAK-2/STAT-3 pathway also mediates the mitogenic effects of insulin, a process recently implicated in AD (Li and Ho¨lscher, 2007). PubMed:19293145

Calcium signaling pathways are involved both in the toxic action of Abeta and in the protection against that toxicity offered by nicotinic ligands. Given that alpha7 homomeric nAChRs are much more permeable to calcium ions than are most other nAChRs (Bertrand et al., 1993), it is to be expected that nicotinic neuroprotection mediated by nAChRs, notably alpha7, would depend upon the activation of calcium signaling pathways. ABT-418 is a nicotinic agonist that protects primary rat cortical neurons from glutamate toxicity through its activation of alpha7 nAChRs, and this is blocked when calcium is removed from the extracellular medium (Donnelly-Roberts et al., 1996). PubMed:19293145