The Role of NLRP3 Inflammasomes in Neurological Disorders: Mechanistic Understanding and Phytochemical-Based...

Neuroinflammation is a well-studied contributor to a number of central nervous system dysfunctions. The nucleotide-binding oligomerisation domain-, leucine-rich repeat-, 38 and pyrin domain-containing 3 (NLRP3) inflammasome is a critical component of the innate immune system that, however, when overactive, can contribute to neuroinflammation. This multiprotein complex is expressed and activated in the central nervous system in response to exogenous and endogenous stimuli, resulting in the activation of Caspase-1. This activation releases pro-inflammatory cytokines such as interleukin-1 (IL-1β) and interleukin-18 (IL-18), which trigger neuronal injury and cell death via multiple downstream signalling pathways. This review explores the implications of the activated NLRP3 inflammasome pathway in neurological, neurodevelopmental, and neuropsychiatric disorders. In addition, phytochemicals having the potential to modulate the activity of the NLRP3 inflammasome, offering therapeutic benefits in the above CNS disorders, have been discussed. However, these phytochemical modulators are still in the experimental phase; more research, including clinical trials, is needed to fully understand their efficacy and safety in human CNS disorders.