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http://dx.doi.org/10.5352/JLS.2021.31.2.237

NLRP3 Inflammasome in Neuroinflammatory Disorders  

Kim, Ji-Hee (BK21Plus Research Group for Longevity and Marine Biotechnology, Pusan National University)
Kim, YoungHee (Department of Molecular Biology, College of Natural Sciences, Pusan National University)
Publication Information
Journal of Life Science / v.31, no.2, 2021 , pp. 237-247 More about this Journal
Abstract
Immune responses in the central nervous system (CNS) function as the host's defense system against pathogens and usually help with repair and regeneration. However, chronic and exaggerated neuroinflammation is detrimental and may create neuronal damage in many cases. The NOD-, LRR-, and pyrin domain―containing 3 (NLRP3) inflammasome, a kind of NOD-like receptor, is a cytosolic multiprotein complex that consists of sensors (NLRP3), adaptors (apoptosis-associated speck like protein containing a caspase recruitment domain, ASC) and effectors (caspase 1). It can detect a broad range of microbial pathogens along with foreign and host-derived danger signals, resulting in the assembly and activation of the NLRP3 inflammasome. Upon activation, NLRP3 inflammasome leads to caspase 1-dependent secretion of the pro-inflammatory cytokines IL-1β and IL-18, as well as to gasdermin D-mediated pyroptotic cell death. NLRP3 inflammasome is highly expressed in CNS-resident cell types, including microglia and astrocytes, and growing evidence suggests that NLRP3 inflammasome is a crucial player in the pathophysiology of several neuroinflammatory and psychiatric diseases, such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, stroke, traumatic brain injury, amyotrophic lateral sclerosis, and major depressive disorder. Thus, this review describes the molecular mechanisms of NLRP3 inflammasome activation and its crucial roles in the pathogenesis of neurological disorders.
Keywords
Neuroinflammation; neuroinflammatory disorders; NLRP3 inflammasome;
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