Nuclear factor-kappa β as a therapeutic target for Alzheimer's disease

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Abstract

Alzheimer's disease (AD) is a typical progressive, chronic neurodegenerative disorder with worldwide prevalence. Its clinical manifestation involves the presence of extracellular plaques and intracellular neurofibrillary tangles (NFTs). NFTs occur in brain tissues as a result of both Aβ agglomeration and Tau phosphorylation. Although there is no known cure for AD, research into possible cures and treatment options continues using cell-cultures and model animals/organisms. The nuclear factor-kappa β (NF-κβ) plays an active role in the progression of AD. Impairment to this signaling module triggers undesirable phenotypic changes such as neuroinflammation, activation of microglia, oxidative stress related complications, and apoptotic cell death. These imbalances further lead to homeostatic abnormalities in the brain or in initial stages of AD essentially pushing normal neurons toward the degeneration process. Interestingly, the role of NF-κβ signaling associated receptor-interacting protein kinase is currently observed in apoptotic and necrotic cell death, and has been reported in brains. Conversely, the NF-κβ signaling pathway has also been reported to be involved in normal brain functioning. This pathway plays a crucial role in maintaining synaptic plasticity and balancing between learning and memory. Since any impairment in the pathways associated with NF-κβ signaling causes altered neuronal dynamics, neurotherapeutics using compounds including, antioxidants, bioflavonoids, and non-steroidal anti-inflammatory drugs against such abnormalities offer possibilities to rectify aberrant excitatory neuronal activity in AD. In this review, we have provided an extensive overview of the crucial role of NF-κβ signaling in normal brain homeostasis. We have also thoroughly outlined several established pathomechanisms associated with NF-κβ pathways in AD, along with their respective therapeutic approaches. (Figure presented.).

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Jha, N. K., Jha, S. K., Kar, R., Nand, P., Swati, K., & Goswami, V. K. (2019, July 1). Nuclear factor-kappa β as a therapeutic target for Alzheimer’s disease. Journal of Neurochemistry. Blackwell Publishing Ltd. https://doi.org/10.1111/jnc.14687

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