Abstract
Several lines of evidence point out the relevance of nucleotide-binding oligomerization domain leucine-rich repeat and pyrin domain-containing protein 3 (NLRP3) inflammasome as a pivotal player in the pathophysiology of several neurological and psychiatric diseases (i.e., Parkinson’s disease (PD), Alzheimer’s disease (AD), multiple sclerosis (MS), amyotrophic lateral sclerosis, and major depressive disorder), metabolic disorders (i.e., obesity and type 2 diabetes) and chronic inflammatory diseases (i.e., intestinal inflammation, arthritis, and gout). Intensive research efforts are being made to achieve an integrated view about the pathophysiological role of NLRP3 inflammasome pathways in such disorders. Evidence is also emerging that the pharmacological modulation of NLRP3 inflammasome by phytochemicals could represent a promising molecular target for the therapeutic management of neurological, psychiatric, metabolic, and inflammatory diseases. The present review article has been intended to provide an integrated and critical overview of the available clinical and experimental evidence about the role of NLRP3 inflammasome in the pathophysiology of neurological, psychiatric, metabolic, and inflammatory diseases, including PD, AD, MS, depression, obesity, type 2 diabetes, arthritis, and intestinal inflammation. Special attention has been paid to highlight and critically discuss current scientific evidence on the effects of phytochemicals on NLRP3 inflammasome pathways and their potential in counteracting central neuroinflammation, metabolic alterations, and immune/inflammatory responses in such diseases.
Highlights
A growing body of evidence highlights the relevance of nucleotide-binding oligomerization domain leucine-rich repeat and pyrin domain-containing protein 3 (NLRP3) inflammasome in the pathophysiology of several autoinflammatory syndromes (i.e., cryopyrin-associated autoinflammatory syndromes (CAPS)), neurological and psychiatric diseases (i.e., Parkinson’s disease (PD), Alzheimer’s disease (AD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and major depressive disorder (MDD)), metabolic disorders, and chronic inflammatory diseases [1,2,3,4]
These results suggest that central NLRP3 overactivation shapes immune/inflammatory responses that contribute to neuroinflammation, microglial activation, neuronal loss, and cognitive and motor impairments in different Central Nervous System (CNS) disorders, and that the pharmacological modulation of this enzymatic complex could represent a suitable way for treatment of such diseases
CNS neuroinflammation in animal models of depression. These authors observed that baicalin (5, 6-dihydroxy-7-O-glucuronide flavonoid glycoside), a major polyphenol compound extracted from Scutellaria radix roots, and salvianolic acid B, a natural compound extracted from Salvia miltiorrhiza, counteracted depressive-like behaviors and central neurogenic/inflammatory responses in rats with chronic unpredictable mild stress (CUMS) and LPS-induced depression, respectively, via direct blockade of NLRP3 inflammasome assembly
Summary
A growing body of evidence highlights the relevance of nucleotide-binding oligomerization domain leucine-rich repeat and pyrin domain-containing protein 3 (NLRP3) inflammasome in the pathophysiology of several autoinflammatory syndromes (i.e., cryopyrin-associated autoinflammatory syndromes (CAPS)), neurological and psychiatric diseases (i.e., Parkinson’s disease (PD), Alzheimer’s disease (AD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and major depressive disorder (MDD)), metabolic disorders (i.e., obesity and type 2 diabetes), and chronic inflammatory diseases (i.e., arthritis and intestinal inflammation) [1,2,3,4]. Given the great interest in the therapeutic potential of phytochemicals, in terms of prevention, cure, and maintenance of remission, intensive efforts are being made to characterize the effects of natural compounds targeting NLRP3 pathways in neurological, metabolic, and inflammatory diseases [11]. In this regard, several studies have shown that various phytochemicals, including polyphenols and glucosinolates, counteract neuroinflammation, metabolic alterations, and immune/inflammatory responses in experimental models of diseases via inhibition of NLRP3 signaling [12,13,14]. Special attention has been paid to highlight and critically discuss current scientific evidence on the effects of phytochemicals on NLRP3 inflammasome pathways and their ability of counteracting central neuroinflammation, metabolic alterations, and immune/inflammatory responses in such diseases
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
