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

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 Ab 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 b (NF-jb) 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-jb signaling associated receptor-interacting protein kinase is currently observed in apoptotic and necrotic cell death, and has been reported in brains. Conversely, the NF-jb 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-jb 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-jb signaling in normal brain homeostasis. We have also thoroughly outlined several established pathomechanisms associated with NF-jb pathways in AD, along with their respective therapeutic approaches.

K284-6111 Alleviates Memory Impairment and Neuroinflammation in Tg2576 Mice by Inhibition of Chitinase-3-like 1 Regulating ERK Dependent PTX3 Pathway

“…Park et al showed that Asiatic acid inhibited methamphetamine-induced neuroin ammation through blocking of ERK pathway [53]. NF-κB could modulate more than 400 different genes including genes engaged in innate immunity and associated with AD [54]. Chen et al demonstrated that BACE1, which is deeply involved in amyloiogenesis, was upregulated when the NF-κB signal was activated [55].…”

Association between DNA Damage and Serum Levels of Copper, Zinc, and Selenium in Full-Term Neonates with Late-Onset Sepsis

“…6 Then, the oxidative stress and other redox cascades initiated by interleukin (IL)-6, IL-8, and nuclear factor kappa-light-chain-enhancer of activated B cells take place, leading to progressive cell damage independent from the causative organisms. 6,25,26 Both Cu and Zn are considered as antioxidant micronutrients, which minimize the inflammatory conditions resulting from oxidative stress. Both elements also play significant roles in the immune system functions including the viability, differentiation, and function of the cells of innate and adaptive response and the production of antibodies.…”

Polyphenols in Alzheimer’s Disease and in the Gut–Brain Axis

“…Polyphenolic antioxidant compounds are mostly plant-derived phenolic compounds-some of which may exist as their ether (e.g., ferulic acid) or ester (e.g., epigallocatechin gallate) derivatives. Polyphenolic compounds are a diverse class of phenolic compounds that include flavanoids, such as epigallocatechin, epigallocatechin gallate, and catechin, and flavonoids, such as quercetin, fisetin, and luteolin, as pharmaceutically important compounds [1][2][3][4]. Quercetin and related flavonoids are β-amyloid precursor protein-cleaving enzyme 1 (BACE-1) inhibitors [5].…”

“…Quercetin and related flavonoids are β-amyloid precursor protein-cleaving enzyme 1 (BACE-1) inhibitors [5]. Flavanoids as well as non-steroidal anti-inflammatory agents (NSAIDS) modulate the nuclear factor-kappa β (NF-κB) signaling pathways, and thereby are potential therapeutic targets for neurodegenerative diseases, such as AD and Parkinson's disease (PD) [2].…”