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Volume 16
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10.3390/brainsci16080792
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Review

Targeting Neutrophil Extracellular Traps in Neuroinflammation: A Therapeutic Perspective on Neurodegenerative Diseases

by
Iolanda Masalskiene Costa
1,
Alexandre Kanashiro
2,3,
Giovanna Siqueira Favi Barros
1,
Ana Julia Monteiro
1,
Caio Santos Bonilha
4,
Giovane Galdino
1,5 and
Flavio Protasio Veras
1,6,*
1
Multicenter Postgraduate Program in Physiological Sciences, Department of Physiological Sciences, Institute of Biomedical Sciences, Federal University of Alfenas, Alfenas 37133-840, MG, Brazil
2
Center for Research in Inflammatory Diseases, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14040-900, SP, Brazil
3
Unidade EMBRAPII—FMRP-USP, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14040-900, SP, Brazil
4
Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow G12 8TA, UK
5
Center for Experimental Biology, Laboratory of Neuroimmunobiology of Pain, Federal University of Alfenas, Alfenas 37133-840, MG, Brazil
6
School of Pharmaceutical Sciences, Federal University of Alfenas, Alfenas 37133-840, MG, Brazil
*
Author to whom correspondence should be addressed.
Brain Sci. 2026, 16(8), 792; https://doi.org/10.3390/brainsci16080792
Submission received: 26 February 2026 / Revised: 23 July 2026 / Accepted: 25 July 2026 / Published: 27 July 2026
(This article belongs to the Section Neuropharmacology and Neuropathology)
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Abstract

Neuroinflammation is a complex process involved in the pathogenesis of several neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, Huntington’s disease, and amyotrophic lateral sclerosis. Neutrophils, although traditionally considered peripheral immune cells, have emerged as active participants in the immunopathology of the central nervous system (CNS) through the release of neutrophil extracellular traps (NETs), structures composed of decondensed chromatin embedded with pro-inflammatory proteins. Evidence suggests that NETs play a dual role: they are protective against pathogens but can also induce tissue damage when produced in excess. Several pathways are involved in their formation, including vesicle-mediated release (vital NETs), the lytic NADPH oxidase (NOX)-dependent pathway, and the mitochondrial pathway. Targeting NETs therapeutically, through the use of NETosis inhibitors, NET-degrading strategies, or blockade of neutrophil migration, has shown promise in reducing neuroinflammation/neurodegeneration and improving neurological outcomes in experimental models. This review aims to investigate both the protective and deleterious roles of NETs and how this knowledge may reveal new therapeutic strategies to modulate neurodegenerative diseases and preserve neural integrity, offering valuable insights for potential applications in clinical practice.
Keywords: neutrophils; neutrophil extracellular traps; neuroinflammation; innate immunity; inflammatory response; neurodegenerative disorders neutrophils; neutrophil extracellular traps; neuroinflammation; innate immunity; inflammatory response; neurodegenerative disorders

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MDPI and ACS Style

Costa, I.M.; Kanashiro, A.; Barros, G.S.F.; Monteiro, A.J.; Bonilha, C.S.; Galdino, G.; Veras, F.P. Targeting Neutrophil Extracellular Traps in Neuroinflammation: A Therapeutic Perspective on Neurodegenerative Diseases. Brain Sci. 2026, 16, 792. https://doi.org/10.3390/brainsci16080792

AMA Style

Costa IM, Kanashiro A, Barros GSF, Monteiro AJ, Bonilha CS, Galdino G, Veras FP. Targeting Neutrophil Extracellular Traps in Neuroinflammation: A Therapeutic Perspective on Neurodegenerative Diseases. Brain Sciences. 2026; 16(8):792. https://doi.org/10.3390/brainsci16080792

Chicago/Turabian Style

Costa, Iolanda Masalskiene, Alexandre Kanashiro, Giovanna Siqueira Favi Barros, Ana Julia Monteiro, Caio Santos Bonilha, Giovane Galdino, and Flavio Protasio Veras. 2026. "Targeting Neutrophil Extracellular Traps in Neuroinflammation: A Therapeutic Perspective on Neurodegenerative Diseases" Brain Sciences 16, no. 8: 792. https://doi.org/10.3390/brainsci16080792

APA Style

Costa, I. M., Kanashiro, A., Barros, G. S. F., Monteiro, A. J., Bonilha, C. S., Galdino, G., & Veras, F. P. (2026). Targeting Neutrophil Extracellular Traps in Neuroinflammation: A Therapeutic Perspective on Neurodegenerative Diseases. Brain Sciences, 16(8), 792. https://doi.org/10.3390/brainsci16080792

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