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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.<\/jats:p>","DOI":"10.3390\/brainsci16080792","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T16:11:56Z","timestamp":1785168716000},"page":"792","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Targeting Neutrophil Extracellular Traps in Neuroinflammation: A Therapeutic Perspective on Neurodegenerative Diseases"],"prefix":"10.3390","volume":"16","author":[{"given":"Iolanda Masalskiene","family":"Costa","sequence":"first","affiliation":[{"name":"Multicenter Postgraduate Program in Physiological Sciences, Department of Physiological Sciences, Institute of Biomedical Sciences, Federal University of Alfenas, Alfenas 37133-840, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Kanashiro","sequence":"additional","affiliation":[{"name":"Center for Research in Inflammatory Diseases, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo, Ribeir\u00e3o Preto 14040-900, SP, Brazil"},{"name":"Unidade EMBRAPII\u2014FMRP-USP, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo, Ribeir\u00e3o Preto 14040-900, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna Siqueira Favi","family":"Barros","sequence":"additional","affiliation":[{"name":"Multicenter Postgraduate Program in Physiological Sciences, Department of Physiological Sciences, Institute of Biomedical Sciences, Federal University of Alfenas, Alfenas 37133-840, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Julia","family":"Monteiro","sequence":"additional","affiliation":[{"name":"Multicenter Postgraduate Program in Physiological Sciences, Department of Physiological Sciences, Institute of Biomedical Sciences, Federal University of Alfenas, Alfenas 37133-840, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1168-8392","authenticated-orcid":false,"given":"Caio Santos","family":"Bonilha","sequence":"additional","affiliation":[{"name":"Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow G12 8TA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovane","family":"Galdino","sequence":"additional","affiliation":[{"name":"Multicenter Postgraduate Program in Physiological Sciences, Department of Physiological Sciences, Institute of Biomedical Sciences, Federal University of Alfenas, Alfenas 37133-840, MG, Brazil"},{"name":"Center for Experimental Biology, Laboratory of Neuroimmunobiology of Pain, Federal University of Alfenas, Alfenas 37133-840, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavio Protasio","family":"Veras","sequence":"additional","affiliation":[{"name":"Multicenter Postgraduate Program in Physiological Sciences, Department of Physiological Sciences, Institute of Biomedical Sciences, Federal University of Alfenas, Alfenas 37133-840, MG, Brazil"},{"name":"School of Pharmaceutical Sciences, Federal University of Alfenas, Alfenas 37133-840, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Bersano, A., Engele, J., and Sch\u00e4fer, M.K.E. 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