Title:Nuclear Factor Kappa-light-chain-enhancer of Activated B Cells (NF-κB) – a Friend, a Foe, or a Bystander - in the Neurodegenerative Cascade and Pathogenesis of Alzheimer's Disease
Volume: 16
Issue: 10
Author(s): Gurdeep Marwarha and Othman Ghribi*
Affiliation:
- Department of Biomedical Sciences, School of Medicine & Health Sciences, University of North Dakota, Grand Forks, ND 58203,United States
Keywords:
Alzheimer's disease, Amyloid-β, synaptic plasticity, learning, memory, neuroinflammation, neuronal death.
Abstract: Background: NF-κB is a ubiquitous transcription factor that was discovered three decades
ago. Since its discovery, this protein complex has been implicated in numerous physiological and
pathophysiological processes such as synaptic plasticity, learning and memory, inflammation, insulin
resistance, and oxidative stress among other factors that are intricately involved and dysregulated in
Alzheimer's disease (AD).
Methods: We embarked on a methodical and an objective review of contemporary literature to integrate
the indispensable physiological functions of NF-κB in neuronal phsyiology with the undesirable
pathophysiological attributes of NF-κB in the etiopathogenesis of Alzheimer's disease. In our approach,
we first introduced Alzheimer's disease and subsequently highlighted the multifaceted roles of
NF-κB in the biological processes altered in the progression of Alzheimer's disease including synaptic
transmission, synaptic plasticity, learning, and memory, neuronal survival and apoptosis, adult neurogenesis,
regulation of neural processes and structural plasticity, inflammation, and Amyloid-β production
and toxicity.
Results: Our comprehensive review highlights and dissects the physiological role of NF-κB from its
pathological role in the brain and delineates both, its beneficial as well as deleterious, role in the etiopathogenesis
of Alzheimer's disease.
Conclusion: In light of our understanding of the duality of the role of NF-κB in the pathogenesis of
Alzheimer's disease, further studies are warranted to dissect and understand the basis of the dichotomous
effects of NF-κB, so that certain selective benevolent and benign attributes of NF-κB can be
spared while targeting its deleterious attributes and facets that are integral in the pathogenesis of Alzheimer's
disease.
