Targeting the NLRP3 Inflammasome in Neuroinflammation: Health Promoting Effects of Dietary Phytochemicals in Neurological Disorders

Abstract

Neurological disorders occur in the central and peripheral nervous system and include Alzheimer's disease, stroke, and spinal cord injury. Activation of the innate immune system inevitably occurs in all forms of neurological disorders. The NOD‐, LRR‐ and pyrin domain‐containing 3 (NLRP3) inflammasome is a multimolecular complex that can sense danger signals associated with neurological disorders. Assembly of the NLRP3 inflammasome promotes caspase‐1‐mediated interleukin‐1β and interleukin‐18 maturation in microglia, where neuroinflammation contributes to neurological disease development and progression. Thus, this review attempts to elucidate the current knowledge regarding NLRP3 inflammasome activation and its crucial role in the pathogenesis of neurological disorders. Recent scientific findings with respect to neuroprotective effects of dietary phytochemicals against NLRP3 inflammasome‐mediated neurological disorders summarized in this review suggest that modulation of the NLRP3 inflammasome assembly by plant‐derived phytochemicals could be a potential strategy for prevention or treatment of neurological disorders.

5‐Heptadecylresorcinol, a Biomarker for Whole Grain Rye Consumption, Ameliorates Cognitive Impairments and Neuroinflammation in APP/PS1 Transgenic Mice

“…Activated microglia can produce cytokines and chemokines that induce astrogliosis, which is a hallmark of neuroinflammation. [ 17 ] Consequently, the proinflammatory mediators could induce a vicious inflammatory cycle, causing neuronal cell dysfunction and death in the brain constantly. [ 18,19 ] Meanwhile, in the central nervous system (CNS), inflammation occurring and progressing can be mediated via activation of the NLRP3 inflammasome, which is a multiprotein complex including NLRP3, ASC, and CASP1.…”

“…Assembly and activation of the NLRP3 inflammasome could result in the generation of activated caspase‐1, and then initiate maturation and secretion of IL‐1β. [ 17 ] Evidence suggests that deficiency of NLRP3 and ASC could decrease Aβ plaque deposition and reduce microglial inflammatory activation both in vitro and in vivo. [ 20 ] Therefore, targeting the NLRP3 inflammasome associated neuroinflammation is an efficient way for neuroprotection.…”

Inhibition of microglial receptor‐interacting protein kinase 1 ameliorates neuroinflammation following cerebral ischaemic stroke

“…45,46 Besides, inhibition of inflammation during ischaemic stroke contributes to reduce ischaemic infarction. 24,30,41 Based on this evidence, we further in- 20 Ma et al demonstrated that rhTrx-1 exerts an antioxidative effect against neurological dysfunction and cerebral infarction. 21 Unlike these studies, we provided a new mechanism by which rhTrx-1 acted as an inhibitor of RIPK1 to reduce cerebral ischaemic injury, and we found inhibition of microglia RIPK1 reduced neuronal apoptosis ( Figure 6).…”

“…ROS accumulation was able to activate the NLRP3 inflammasome, and the activated NLRP3 inflammasome subsequently mediated neuroinflammation during ischaemic stroke by secretion IL‐1β. Deficiency of NLRP3 significantly alleviated neuroinflammation in ischaemic stroke and ischaemic injury 41 . It has been reported that RIPK1 can trigger the activation of the NLRP3 inflammasome by disrupting the mitochondrial membrane integrity and by promoting the release of ROS, which further promotes the production and secretion of IL‐1β to the extracellular space and initiates neuroinflammation.…”

<p>Spinal TLR4/P2X7 Receptor-Dependent NLRP3 Inflammasome Activation Contributes to the Development of Tolerance to Morphine-Induced Antinociception</p>

“…The Nod-like receptor protein 3 (NLRP3) inflammasome has been demonstrated to be crucial for the regulation of microglia-mediated neuroinflammation. 8,9 It consists of a cytosolic multiprotein complex, composed of NLRP3, apoptosis-associated speck-like protein (ASC), and procaspase-1, and can be activated by a wide range of exogenous and endogenous stimuli. 10 The activation of the NLRP3 inflammasome involves a two-step process.…”