Department of Pharmacy, Southeast University, Dhaka, Bangladesh.
Department of Human Nutrition, The University of Agriculture Peshawar, Khyber Pakhtunkhwa, Pakistan.
Curr Pharm Des. 2021;27(3):402-414. doi: 10.2174/1381612826666201118092422.
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 have been found yet. Over the last few decades, research on AD has mainly highlighted 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 shows a promising candidate for inflammation- based AD therapy. Recent data reveal that phytochemicals, mainly polyphenol compounds, exhibit potential neuroprotective functions and these 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.
阿尔茨海默病(AD)是一种不可逆转的慢性脑部疾病,其特征是神经元丧失、小胶质细胞积累和进行性认知障碍。这种危及生命的疾病的适当病理生理学尚未完全了解,也尚未找到确切的治疗方法。在过去的几十年中,AD 的研究主要强调了与几种主要病理特征相关的病理机制,包括由淀粉样β(Aβ)肽组成的细胞外老年斑,以及由 tau 蛋白组成的细胞内神经原纤维缠结(NFTs)。Aβ 可诱导细胞凋亡、引发炎症反应、抑制海马突触可塑性,最终导致认知功能下降和记忆障碍。最近,由脑固有免疫细胞介导的神经炎症反应,作为第三种疾病特征,成为当前研究领域的焦点,这一观点得到了临床前、临床和遗传研究的证实。核因子 kappa-轻链增强子的 B 细胞(NF-κB)是一种细胞因子产生物,与生理炎症过程显著相关,因此被认为是基于炎症的 AD 治疗的一个有前途的候选物。最近的数据表明,植物化学物质,主要是多酚化合物,具有潜在的神经保护功能,这些物质可能被认为是发现几种 AD 药物候选物的重要资源。有趣的是,植物化学物质可以很容易地干扰 NF-κB 的信号通路。本综述代表了多酚类化合物作为 NF-κB 抑制剂的抗神经炎症潜力,以对抗 AD 的发病机制。