Targeting Nlrp3 Inflammasomes: A Trojan Horse Strategy for Intervention in Neurological Disorders Publisher Pubmed



Tork MAB^{1, 4} ; Fotouhi S² ; Roozi P³ ; Negah SS^{1, 4, 5, 6} Show Affiliations
Source: Molecular Neurobiology Published:2025

Abstract

Recently, a growing focus has been on identifying critical mechanisms in neurological diseases that trigger a cascade of events, making it easier to target them effectively. One such mechanism is the inflammasome, an essential component of the immune response system that plays a crucial role in disease progression. The NLRP3 (nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain containing 3) inflammasome is a subcellular multiprotein complex that is widely expressed in the central nervous system (CNS) and can be activated by a variety of external and internal stimuli. When activated, the NLRP3 inflammasome triggers the production of proinflammatory cytokines interleukin-1β (IL-1β) and interleukin-18 (IL-18) and facilitates rapid cell death by assembling the inflammasome. These cytokines initiate inflammatory responses through various downstream signaling pathways, leading to damage to neurons. Therefore, the NLRP3 inflammasome is considered a significant contributor to the development of neuroinflammation. To counter the damage caused by NLRP3 inflammasome activation, researchers have investigated various interventions such as small molecules, antibodies, and cellular and gene therapy to regulate inflammasome activity. For instance, recent studies indicate that substances like micro-RNAs (e.g., miR-29c and mR-190) and drugs such as melatonin can reduce neuronal damage and suppress neuroinflammation through NLRP3. Furthermore, the transplantation of bone marrow mesenchymal stem cells resulted in a significant reduction in the levels of pyroptosis-related proteins NLRP3, caspase-1, IL-1β, and IL-18. However, it would benefit future research to have an in-depth review of the pharmacological and biological interventions targeting inflammasome activity. Therefore, our review of current evidence demonstrates that targeting NLRP3 inflammasomes could be a pivotal approach for intervention in neurological disorders. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2024.