SECUAH 2025 > Fernández-Vega etal 2025

dianas | Vol 14 No 1 | marzo 2025 | e202503x013

Inflammation and Neurodegeneration in Multiple Sclerosis: The Role of Neutrophils, NETs, and the NLRP3 Inflammasome

Eva Fernández-Vega^1,a, Juan Mozas-Gutiérrez^2,b, Irene Cuadrado Berrocal^1,c, Raquel Reyes Manzanas^2,d

1. Dpto. de Farmacología, Farmacognosia y Botánica, Facultad de Farmacia, Universidad Complutense de Madrid. Pl. de Ramón y Cajal, s/n, Moncloa - Aravaca, 28040 Madrid.  2. Dpto. de Inmunología, Oftalmología y Otorrinolaringología, Facultad de Medicina, Universidad Complutense de Madrid. Pl. de Ramón y Cajal, s/n, Moncloa - Aravaca, 28040 Madrid. 

a. evfern08@ucm.es  b. jmozas01@ucm.es  c. icberrocal@ucm.es  d. raqrey02@ucm.es 

X Congreso de Señalización Celular, SECUAH 2024.
XIX Simposio de Dianas Terapéuticas.
17 a 21 de marzo, 2025. Universidad de Alcalá. Alcalá de Henares, Madrid. España.

Keywords: Multiple Sclerosis; NLRP3; inflammasome; NETs; NETosis; neutrophils

Abstract

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) characterized by progressive axonal demyelination and neurodegeneration. While the immune response in MS is primarily mediated by T lymphocytes and macrophages, growing evidence highlights the pivotal role of neutrophils in disease pathogenesis. In particular, these cells contribute to neuroinflammation through the formation of Neutrophil Extracellular Traps (NETs), which have been strongly associated with the activation of the NLRP3 inflammasome. Both mechanisms, initially recognized for their antimicrobial and inflammatory functions, have been implicated in the exacerbation of CNS damage, particularly through the destruction of the myelin sheath.
Moreover, activation of the NLRP3 inflammasome amplifies the inflammatory response by promoting neutrophil activation, enhancing NETosis, and inducing the release of key pro-inflammatory cytokines such as IL-1β and IL-18. These processes create a self-perpetuating inflammatory loop that significantly contributes to disease progression. In this context, experimental autoimmune encephalomyelitis (EAE), the most widely used animal model for MS, has provided valuable insights into the relevance of these mechanisms. Given the growing recognition of their pathogenic role, both the NLRP3 inflammasome and NETs have emerged as promising therapeutic targets. Future research focusing on their modulation could pave the way for the development of novel treatment strategies aimed at mitigating neuroinflammation and slowing disease progression.