PubMed 28745240

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

PubMed 28745240

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

PubMed 28745240

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

PubMed 28745240

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

PubMed 28745240

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

PubMed 25652642

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

PubMed 25652642

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

BEL
a(CHEBI:"amyloid-beta") positiveCorrelation act(complex(GO:"NF-kappaB complex"))
Hash
bce2aea2e6
MeSHDisease
Alzheimer Disease
Networks

PubMed 25652642

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

BEL
a(CHEBI:"amyloid-beta") decreases act(complex(GO:"NF-kappaB complex"))
Hash
a94888bfb5
MeSHDisease
Alzheimer Disease
Networks

PubMed 25652642

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

BEL
a(CHEBI:"amyloid-beta") increases act(complex(GO:"NF-kappaB complex"))
Hash
74534872e2
MeSHAnatomy
Neurons, Neuroglia
MeSHDisease
Alzheimer Disease
Networks

About

BEL Commons is developed and maintained in an academic capacity by Charles Tapley Hoyt and Daniel Domingo-Fernández at the Fraunhofer SCAI Department of Bioinformatics with support from the IMI project, AETIONOMY. It is built on top of PyBEL, an open source project. Please feel free to contact us here to give us feedback or report any issues. Also, see our Publishing Notes and Data Protection information.

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.