The relationship between neurodevelopmental disorders (NDDs) and NLRP3 inflammasome

Inflamm Res. 2025 Jun 3;74(1):90. doi: 10.1007/s00011-025-02052-1.

Abstract

The brain's process of creating neural networks that affect functionality or performance is referred to as neurodevelopment. A person's capacity to learn and remember, pay attention, regulate their emotions, socialize, exercise and self-control are just a few of the cognitive and motor abilities that can be affected by abnormal brain development. Numerous neurodevelopmental diseases have been functionally related to abnormalities in innate immune signaling networks. Innate immunity is in charge of the defense of humans against pathogens and tissue damage by triggering inflammation, mainly through sensing pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). Some of these inflammatory processes have been shown to be mediated by large multiprotein complexes called inflammasomes which are present in cytosol and play important roles in the immune system. Due to its role in defense against infectious agents, bacteria, viruses, and fungi, NLRP3 is almost the most studied and well-known member of inflammasomes. The involvement of NLRP3 in inflammatory illnesses is evident due to the wide range of triggers and its intricate signaling pathways. In disorders with neurodevelopmental underpinnings, such as autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), schizophrenia (SCZ), obsessive compulsive disorder (OCD), bipolar disorder (BD), Tourette syndrome (TS), etc., neuroinflammation plays a significant role in their pathophysiology. For these reasons, we reviewed the roles of NLRP3 in various neurodevelopmental disorders below.

Keywords: Autism spectrum disorder; Bipolar disorder; NLRP3; Neurodevelopment; Schizophrenia.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Inflammasomes* / immunology
  • NLR Family, Pyrin Domain-Containing 3 Protein* / immunology
  • Neurodevelopmental Disorders* / immunology

Substances

  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP3 protein, human