MINI REVIEW article
Front. Immunol.
Sec. Multiple Sclerosis and Neuroimmunology
This article is part of the Research TopicThe role of Inflammasome in Neuroinflammation and NeurodegenerationView all 4 articles
Neuroimmune modulatory effects of the NLRP3 inflammasome: the role of sex and living environment in brain affecting conditions
Provisionally accepted
- 1Department of Life Science, University of Modena and Reggio Emilia, Modena, Italy
- 2Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy
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The NLRP3 inflammasome is a master regulator of neuroinflammation, linking systemic perturbations to brain dysfunction and thereby influencing overall brain health. Its sensitivity to biological sex and environmental factors suggests that NLRP3 may act both as a contributor to sex-dependent disease mechanisms and a modifiable therapeutic target for pharmacological and non-pharmacological interventions. In this mini-review, we summarize emerging evidence on sex-specific differences in NLRP3 signaling that may contribute to disparities between males and females in disease incidence, symptomatology, and treatment response. Neuroinflammation-driven disorders, including atherosclerosis, neuropathic pain, substance use, and stress-related syndromes, show how sex influences NLRP3 inflammasome expression and activity with downstream effects on cognition and behavior. We also examine the modulatory influence of environmental factors, with emphasis on social behavior and environmental enrichment, as determinants of NLRP3 dynamics relevant to neurocognitive function and brain health. Overall, the findings suggest that NLRP3 acts as a central hub integrating sex and environmental influences, with broad implications for personalized interventions in brain-related disorders.
Keywords: NLRP3 inflammasome, Biological sex, Central Nervous System, Social Isolation, enriched environment, Exposome, Pharmacology
Received: 23 Sep 2025; Accepted: 29 Oct 2025.
Copyright: © 2025 Ciani, Rigillo, Bertarini, Benatti, Alboni and TASCEDDA. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Giovanna Rigillo, giovanna.rigillo@unimore.it
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