NET-targeted therapy: effects, limitations, and potential strategies to enhance treatment efficacy

Bonilha, Caio S.; Veras, Flávio P.; Cunha, Fernando

doi:10.1016/j.tips.2023.06.007

Cited by 8 publications

(2 citation statements)

References 77 publications

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“…However, they can lead to pathophysiological mechanisms if produced excessively or not efficiently removed 42 . As a result, new therapeutic strategies have been investigated to inhibit or delay the release of NETs 43 .…”

Section: Discussionmentioning

confidence: 99%

Resveratrol prevents the release of neutrophil extracellular traps (NETs) by controlling hydrogen peroxide levels and nuclear elastase migration

de Mattos,

Formiga-Jr,

Saraiva

2024

Sci Rep

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Neutrophil extracellular traps (NETs) are defense mechanisms that trap and kill microorganisms and degrade cytokines. However, excessive production, dysregulation of suppression mechanisms, or inefficient removal of NETs can contribute to increased inflammatory response and the development of pathological conditions. Therefore, research has focused on identifying drugs that inhibit or delay the NET release process. Since reactive oxygen species (ROS) play a significant role in NET release, we aimed to investigate whether resveratrol (RSV), with a wide range of biological and pharmacological properties, could modulate NET release in response to different stimuli. Thus, human neutrophils were pretreated with RSV and subsequently stimulated with PMA, LPS, IL-8, or Leishmania. Our findings revealed that RSV reduced the release of NETs in response to all tested stimuli. RSV decreased hydrogen peroxide levels in PMA- and LPS-stimulated neutrophils, inhibited myeloperoxidase activity, and altered the localization of neutrophil elastase. RSV inhibition of NET generation was not mediated through A2A or A2B adenosine receptors or PKA. Based on the observed effectiveness of RSV in inhibiting NET release, our study suggests that this flavonoid holds potential as a candidate for treating NETs involving pathologies.

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Section: Discussionmentioning

confidence: 99%

Resveratrol prevents the release of neutrophil extracellular traps (NETs) by controlling hydrogen peroxide levels and nuclear elastase migration

de Mattos,

Formiga-Jr,

Saraiva

2024

Sci Rep

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“…A nano drug delivery system may represent a potential solution. 208 Nanodelivery systems and their active targeting strategy would greatly improve the stability and effectiveness of NETs inhibitors. In this section, we summarize recent nano-drug delivery strategies for targeting of NETs (Table 3).…”

Section: Nanodelivery Systemsmentioning

confidence: 99%

Role and Therapeutic Targeting Strategies of Neutrophil Extracellular Traps in Inflammation

Li,

Xiao,

Filipczak

et al. 2023

IJN

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Neutrophil extracellular traps (NETs) are large DNA reticular structures secreted by neutrophils and decorated with histones and antimicrobial proteins. As a key mechanism for neutrophils to resist microbial invasion, NETs play an important role in the killing of microorganisms (bacteria, fungi, and viruses). Although NETs are mostly known for mediating microbial killing, increasing evidence suggests that excessive NETs induced by stimulation of physical and chemical components, microorganisms, and pathological factors can exacerbate inflammation and organ damage. This review summarizes the induction and role of NETs in inflammation and focuses on the strategies of inhibiting NETosis and the mechanisms involved in pathogen evasion of NETs. Furthermore, herbal medicine inhibitors and nanodelivery strategies improve the efficiency of inhibition of excessive levels of NETs.

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An elastase nanocomplex with metal cofactors for enhancement of target protein cleavage activity and synergistic antitumor effect

Zhu,

Chen,

Gong

et al. 2024

Chemical Engineering Journal

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NET-targeted therapy: effects, limitations, and potential strategies to enhance treatment efficacy

Cited by 8 publications

References 77 publications

Resveratrol prevents the release of neutrophil extracellular traps (NETs) by controlling hydrogen peroxide levels and nuclear elastase migration

Resveratrol prevents the release of neutrophil extracellular traps (NETs) by controlling hydrogen peroxide levels and nuclear elastase migration

Role and Therapeutic Targeting Strategies of Neutrophil Extracellular Traps in Inflammation

An elastase nanocomplex with metal cofactors for enhancement of target protein cleavage activity and synergistic antitumor effect

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