Targeting NINJ1-mediated cell rupture to treat inflammatory diseases

Molecular Medicine, Journal Year: 2025, Volume and Issue: 31(1)

Published: Feb. 14, 2025

Abstract Cell death can terminate in plasma membrane rupture to release potent pro-inflammatory intracellular contents thereby contributing inflammatory diseases. is an active process, mediated by the protein ninjurin-1 (NINJ1) pyroptosis, post-apoptosis lysis, ferroptosis, and forms of necrosis. Once activated, NINJ1 clusters into large oligomers within initiate cellular lysis. Recent preclinical studies have demonstrated that inhibiting a new strategy for treating immune-mediated Indeed, both small molecule inhibitors neutralizing antibodies target clustering preserve integrity mitigate disease pathogenesis. In this Perspective , we provide summary current state knowledge recent developments targeting during cell through inhibition treat disease, with focus on liver injury. As these NINJ1-mediated pathways are pivotal maintaining health contribute pathogenesis when dysregulated, discussed broad implications across immunologic basis molecular medicine.

Language: Английский

Role of Histone Deacetylases in Drug-Resistant Melanoma: Mechanisms and Therapeutic Implications

Kinases and Phosphatases, Journal Year: 2025, Volume and Issue: 3(2), P. 8 - 8

Published: April 21, 2025

Melanoma, known for its aggressive nature and propensity developing drug resistance, remains a significant clinical challenge. The emergence of resistance to both targeted therapies (like BRAF/MEK inhibitors) immunotherapies is major obstacle achieving durable responses improving patient survival. HDACs, class epigenetic enzymes, modulate gene expression chromatin structure by removing acetyl groups from histone non-histone proteins. In melanoma, aberrant HDAC activity contributes through multiple mechanisms. HDACs influence key oncogenic signaling pathways frequently dysregulated in such as the MAPK, PI3K/AKT, WNT/β-catenin cascades. By altering these pathways, promote survival proliferation melanoma cells even presence therapy. Beyond their direct effects on tumor cells, also play crucial role shaping microenvironment. They can suppress anti-tumor immune reducing cell infiltration, modulating cytokine production, fostering an immunosuppressive milieu. This further immunotherapies. Given central mechanisms, inhibitors (HDACis) have emerged potential therapeutic agents restore sensitivity. HDACis induce death, inhibit proliferation, enhance cells. Preclinical studies explored combination with existing overcome resistance. While promising, application accompanied challenges, including toxicity, need biomarkers predict response, optimization strategies. Ongoing research dedicated more selective potent better understand how effectively incorporate them into treatment regimens. review provides comprehensive overview multifaceted ways which contribute discusses HDAC-targeted improve outcomes.

Language: Английский