Evidences a(CHEBI:"amyloid-beta") to complex(GO:"NF-kappaB complex")

Recent evidence has cogently shown that Amyloid-β induces apoptosis in rat primary neurons and human post-mitotic neuronal cells by reducing Bcl-XL expression level and evoking the release of cytochrome c from the mitochondria in a NF-κB – dependent manner

Furthermore, fibrillar Amyloid-β has been shown to activate NF-κB via the assembly pf the C5b-MAC complex

Furthermore, Amyloid-β actuates NF-κB – dependent pro-inflammatory pathways in microglia culminating in TNFα expression and subsequently TNFα effectuated neurotoxicity

In primary neuronal cultures, Amyloid-β has been shown to elicit oxidative stress and evoke NF-κB activation

Furthermore, Amyloid-β –induced NF-κB also results in the up-regulation of the antioxidant mitochondrial membrane enzyme – MnSOD (superoxide dismutase 2) [328] which is well known to combat oxidative stress and apoptosis

Under physiological conditions activation of NF-κB by endogenous Aβ reduces βAPP, BACE1 and the γ-secretase activity, thereby lowering Aβ processing and facilitating Aβ homeostasis

However in AD, exposure to high Aβ concentrations upregulates NF-κB activation increasing βAPP and Aβ processing, precipitating a feed-back loop that favor exacerbated Aβ production

Mechanistically, the Aβ induced neuronal apoptosis has been attributed to the increase in the ratio of proapoptotic gene (BAX) transcription to that of the anti-apoptotic gene Bcl-Xl, and/or to the reduction in constitutively activated NF-κB with consequent increase in the cytoplasmic IκB proteins

This is supported by the observation that in mixed neuronal-glial cell cultures, Aβ induces increasing degree of neurotoxicity in an NF-κB dependent manner in the presence of higher proportion of glial cells

Multiple studies have cogently shown that the inhibition of NF-κB activity results in the mitigation of secreted Amyloid-β by cultured cells in vitro

NF-κB is also widely implicated in the engenderment of Amyloid-β in vivo in a multitude of mouse models

A multitude of studies have demonstrated that NF-κB directly regulates the transcription and expression of BACE1, thereby eliciting profound effects on AβPP processing and engenderment of Amyloid-β

Indeed, Checler and colleagues have shown in a recent study that, NF-κB mediates the Amyloid-β – induced increase in expression of AβPP in HEK293 cells

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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.