The NLRP3 inflammasome: pathophysiology and therapeutic implications for schizophrenia and neuropsychiatric disorders

Schizophrenia is a complex psychiatric disorder with an incompletely understood etiology, but converging evidence supports a role for chronic neuroinflammation in its pathogenesis. The nucleotide-binding oligomerization domain-, leucine-rich repeat and pyrin domain-containing 3 (NLRP3) inflammasome is a central regulator of innate immune responses in the central nervous system and has been implicated in several neuropsychiatric disorders. Emerging evidence links dysregulated NLRP3 activity to inflammatory and structural brain changes relevant to schizophrenia, though direct clinical evidence remains limited and causal relationships have not been established. The goals of this review are to: (1) summarize the biology of the NLRP3 inflammasome and its role in neuroinflammation, (2) evaluate evidence for NLRP3 dysregulation in schizophrenia and related neuropsychiatric disorders, (3) examine NLRP3 inhibitors tested in neuropsychiatric conditions and assess their translational relevance to schizophrenia, and (4) critically appraise the potential of NLRP3 as a peripheral and central biomarker of schizophrenia, identifying key gaps that future research must address.