Polyphenols Targeting NF-κB Pathway in Neurological Disorders: What We Know So Far?

Abstract

Polyphenolic compounds have shown promising neuroprotective properties, making them a valuable resource for identifying prospective drug candidates to treat several neurological disorders (NDs). Numerous studies have reported that polyphenols can disrupt the nuclear factor kappa B(NF-κB) pathway by inhibiting the phosphorylation or ubiquitination of signaling molecules, which further prevents the degradation of IκB. Additionally, they prevent NF-κB translocation to the nucleus and pro-inflammatory cytokine production. Polyphenols such as curcumin, resveratrol, and pterostilbene had significant inhibitory effects on NF-κB, making them promising candidates for treating NDs. Recent experimental findings suggest that polyphenols possess a wide range of pharmacological properties. Notably, much attention has been directed towards their potential therapeutic effects in NDs such as Alzheimer's disease (AD), Parkinson's disease (PD), cerebral ischemia, anxiety, depression, autism, and spinal cord injury (SCI). Much preclinical data supporting the neurotherapeutic benefits of polyphenols has been developed. Nevertheless, this study has described the significance of polyphenols as potential neurotherapeutic agents, specifically emphasizing their impact on the NF-κB pathway. This article offers a comprehensive analysis of the involvement of polyphenols in NDs, including both preclinical and clinical perspectives.

Keywords: Alzheimer's disease; NF-κB pathway; Neuroinflammation; Parkinson's disease; Polyphenols; neurological disorders; spinal cord injury.

Figure 1

Illustration represents the polyphenols targeting the NF-κB pathway associated with Alzheimer's disease. Inappropriate breakdown of amyloid precursor protein by beta and gamma-secretase results in the creation of amyloid-beta plaque, which in turn leads to mitochondrial malfunction and apoptosis, which ultimately results in Alzheimer's disease. Cytokines and toxins also are responsible for activating the NF-κB pathway, which ultimately results in inflammation in the nervous system and ultimately leads to Alzheimer's disease state.

Figure 2

Illustration represents the polyphenols targeting the NF-κB pathway associated with Parkinson's disease. The activation of the NF-κB, MAPK, and Nrf2 pathways by amyloid-beta plaque and neurofibrillary tangles ultimately results in the leaking of the blood-brain barrier (BBB) and neuroinflammation, which ultimately leads to Parkinson's disease.

Figure 3

Illustration represents the polyphenols targeting the NF-κB pathway associated with SCI. SCI is characterized by primary injury followed by secondary injury. Increased intracellular calcium ion concentration, free radical production, blood-spinal cord barrier disruption, and mass ion reflux result from primary injuries, leading to the progression of secondary injuries. In addition, spinal ischemia, oxidative stress, and neuroinflammation lead to the progression of secondary SCI.

Figure 4

Structures of bioactive polyphenolic compounds effective in NF-κB signaling pathway-associated neurological disorders