Mixed lineage kinase domain-like protein in liver diseases: Cell-type-specific functions and dual roles DOI
Ming‐Xing Liang, Ying Zhou, Shuren Li

et al.

World Journal of Gastroenterology, Journal Year: 2025, Volume and Issue: 31(14)

Published: April 9, 2025

In this letter, we comment on the article by Xuan Yuan et al, published in recent issue of World Journal Gastroenterology. Mixed lineage kinase domain-like protein (MLKL) exhibits cell-type-specific functions liver parenchymal and non-parenchymal cells, playing dual roles pathogenesis diseases. hepatocytes, MLKL primarily mediates necroptosis inhibits autophagy, thereby exacerbating injury. Conversely, modulates inflammatory responses promotes fibrotic processes, driving disease progression. Notably, also demonstrates protective under specific conditions. For instance, can inhibit intracellular bacterial replication, promote endosomal trafficking, facilitate generation release extracellular vesicles, potentially exerting hepatoprotective effects. Understanding these mechanisms action, including its promoting injury providing protection, is crucial for elucidating complex diseases developing targeted therapeutic strategies.

Language: Английский

Targeting mixed lineage kinase domain-like protein's non-necroptosis role: A new horizon in anti-inflammatory therapy for alcoholic liver disease DOI
Yue Xi, Dong Guo, Li Shi

et al.

World Journal of Gastroenterology, Journal Year: 2025, Volume and Issue: 31(13)

Published: April 2, 2025

Although mixed lineage kinase domain-like protein (MLKL) is widely recognized as a critical effector in the necroptotic signaling pathway, MLKL plays broader regulatory roles beyond programmed necroptosis. Notably, Xuan Yuan et al demonstrated that CPD4, an ATP-binding pocket inhibitor of MLKL, significantly reduces liver inflammation and improves function by inhibiting NF-κB signaling, suggesting its use potential therapeutic candidate for alcoholic disease. However, pharmacokinetic properties long-term toxicity CPD4 require further evaluation. Moreover, single strategy targeting may not be sufficient. Future studies should focus on precise regulation develop combination therapies to achieve dual intervention inflammatory cell death pathways. This paper provides important theoretical foundation translational research MLKL-targeted therapy. clinical translation requires overcoming existing limitations elucidating network complex microenvironments.

Language: Английский

Citations

0
Mixed lineage kinase domain-like protein in liver diseases: Cell-type-specific functions and dual roles DOI
Ming‐Xing Liang, Ying Zhou, Shuren Li

et al.

World Journal of Gastroenterology, Journal Year: 2025, Volume and Issue: 31(14)

Published: April 9, 2025

In this letter, we comment on the article by Xuan Yuan et al, published in recent issue of World Journal Gastroenterology. Mixed lineage kinase domain-like protein (MLKL) exhibits cell-type-specific functions liver parenchymal and non-parenchymal cells, playing dual roles pathogenesis diseases. hepatocytes, MLKL primarily mediates necroptosis inhibits autophagy, thereby exacerbating injury. Conversely, modulates inflammatory responses promotes fibrotic processes, driving disease progression. Notably, also demonstrates protective under specific conditions. For instance, can inhibit intracellular bacterial replication, promote endosomal trafficking, facilitate generation release extracellular vesicles, potentially exerting hepatoprotective effects. Understanding these mechanisms action, including its promoting injury providing protection, is crucial for elucidating complex diseases developing targeted therapeutic strategies.

Language: Английский

Citations

0