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

In addition, not only have alpha7 nAChRs been found colocalized with plaques (Wang et al., 2000b) but alpha7 and alpha4 subunits are also positively correlated with neurons that accumulate Abeta (Wevers et al., 1999).

Curiously, although most studies are in agreement that nAChRs need to be activated to mediate their protective effects, mouse cortical neurons are protected by the alpha7 antagonist methyllycaconitine (Martin et al., 2004), raising the possibility that neuroprotection by alpha7 agonists may be through desensitization rather than activation of this rapidly desensitizing receptor. This would be consistent with the alpha7- dependent activation of intracellular signaling pathways by Abeta (Bell et al., 2004), but the opposite effects on cell survival exerted by Abeta and nicotine means that other mechanisms must be sought, such as ligand-specific coupling to downstream signaling pathways.

In contrast, Small et al. (2007) found no displacement of alpha-BTX from SH-SY5Y cells (a cell line very closely related to that used by Wang et al.) by either amyloid or methyllycaconitine. Wang et al. (2000b) also showed similar staining of human AD cortical neurons by alpha7 and Abeta antibodies in double immunofluorescence, suggesting that in human cortical neurons, alpha7 and Abeta are closely associated, although such an approach does not prove direct binding. However another study (Small et al., 2007) showed no displacement of labeled alpha-bungarotoxin from cell lines expressing rat alpha7 nAChRs.

Abeta action on nAChRs depends on subunit composition; it has been reported to block alpha7, transiently potentiate alpha4beta2 before blocking, and to have no action on alpha3beta4 (Pym et al., 2005). However, in contrast to its reported transient enhancement when expressed in oocytes, an inhibition of alpha4beta2 has been reported when expressed in human SH-EP1 cells (Wu et al., 2004).

Again, despite numerous reports of a block of alpha7, one study indicated that Abeta failed to block alpha7, even though it blocked alpha4beta2, alpha2beta2 and alpha4alpha5beta2 receptors (Lamb et al., 2005).

It has also been observed that although Abeta inhibits recombinant human and mouse alpha7 nAChRs, transgenic mice overexpressing human Abeta express functional alpha7 nAChRs, and the amplitude of alpha7- mediated currents is no different from that of wild-type mice (Spencer et al., 2006).

Similar effects of Abeta on nAChR expression have been confirmed in studies using cultured cells; Abeta causes a reduced expression of nAChRs in PC12 cells (Guan et al., 2001), and alpha4, alpha3, and alpha7 expression are all increased in cultured rat astrocytes (Xiu et al., 2005).

This prospect was supported by the finding that α7 nAChRs were found in plaques (159), and α7 and α4 subunits positively correlated with neurons that accumulated Aβ and hyperphosphorylated tau in AD brain tissue (161).

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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.