Anti-Neuroinflammatory Potential of Polyphenols by Inhibiting NF-κB to Halt Alzheimer's Disease

Abstract

: Alzheimer's disease (AD) is an irrevocable chronic brain disorder featured by neuronal loss, microglial accumulation, and progressive cognitive impairment. The proper pathophysiology of this life-threatening disorder is not completely understood and no exact remedies are found yet. Over the last few decades, research on AD has mainly highlighted in pathomechanisms linked to a couple of the major pathological hallmarks, including extracellular senile plaques, made of amyloid-β (Aβ) peptides, and intracellular neurofibrillary tangles (NFTs), made of tau proteins. Aβ can induce apoptosis, trigger an inflammatory response, and inhibit the synaptic plasticity of the hippocampus, which ultimately contributes to reducing cognitive functions and memory impairment. Recently, a third disease hallmark, the neuroinflammatory reaction that is mediated by cerebral innate immune cells, has become a spotlight in the current research area, assured by pre-clinical, clinical, and genetic investigations. Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), a cytokine producer, is significantly associated with physiological inflammatory proceedings and thus showing a promising candidate for inflammation-based AD therapy. Recent data reveal that phytochemicals mainly polyphenols compounds exhibit potential neuroprotective functions and it may be considered as a vital resource for discovering several drug candidates against AD. Interestingly, phytochemicals can easily interfere with the signaling pathway of NF-κB. This review represents the anti-neuroinflammatory potential of polyphenols as inhibitors of NF-κB to combat AD pathogenesis.

Bioactive Compounds and Their Derivatives: An Insight into Prospective Phytotherapeutic Approach against Alzheimer’s Disease

“…[ 144 , 145 ]. Its activation has been associated with A β -initiated neurotoxicity [ 146 ], and it has been found in the brains of Alzheimer's patients [ 147 ]. Natural substances can hinder AD neurodegeneration with fewer adverse effects than synthetic medications.…”

Aplysia Neurons as a Model of Alzheimer’s Disease: Shared Genes and Differential Expression

“…Increased activation of proinflammatory signaling cascades recruited by the ISR has also been demonstrated to be increased in AD (Colangelo et al 2002). Positive feedback of this proinflammatory loop has been proposed to induce chronic neuroinflammation and contribute to neurodegenerative consequences in AD (Jones and Kounatidis 2017;Ju Hwang et al 2019;Lindsay et al 2021;Uddin et al 2021). For example, induction of miRNAs by NF-κB in AD directly results in the downregulation of previously discussed SYN2 (Lukiw 2012).…”

The Use of Bioactive Compounds in Hyperglycemia- and Amyloid Fibrils-Induced Toxicity in Type 2 Diabetes and Alzheimer’s Disease

“…In pheochromocytom PC12 cells, OA improved catalase and SOD activities, attenuated release of IL-6 and TNF-α and decreased malondialdehyde formation [231]. When OA extracts from Aralia cordata were added to cultured rat cortical neurons, it inhibited neuronal death, glutamate release, and generation of ROS induced by Aβ-peptide (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) [232]. In mouse models, OA administration improved memory loss, alleviated neuronal damage and synapse changes in Aβ25-35-induced AD mouse models [233].…”

“…However, an abnormal phosphorylation of Akt substrates was observed in AD brain implying that therapeutics directed to activate the Akt pathway requires prudence in neurodegenerative diseases [26]. On the other hand, models of AD [27] and T2DM [28] showed significant improvements following downregulation of inflammatory responses. Recent data revealed that small bioactive compounds exhibit potential protective functions and may be considered as alternative resource for pharmaceutical drug design against insulin resistance-related disease, providing new direction in drug discovery.…”