NLRP3 Negative Regulation Mechanisms in the Resting State and Its Implications for Therapeutic Development DOI Open Access
Yeji Kim, Sumin Lee, Yong Hwan Park

и другие.

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(16), С. 9018 - 9018

Опубликована: Авг. 20, 2024

The NACHT-, leucine-rich-repeat-, and pyrin domain-containing protein 3 (NLRP3) is a critical intracellular sensor of the innate immune system that detects various pathogen- danger-associated molecular patterns, leading to assembly NLRP3 inflammasome release interleukin (IL) 1β IL-18. However, abnormal activation has been implicated in pathogenesis autoinflammatory diseases such as cryopyrin-associated syndromes (CAPS) common Alzheimer's disease asthma. Recent studies have revealed functions an indirect sensor, similar plant guard system, regulated by binding inhibitory 14-3-3 proteins. Upon activation, transitions its active form. predicted follow regulatory mechanism maintain inactive form cage model, it also acts sensor. Additionally, newly developed inhibitors found inhibit activity stabilizing Most reviews on focused inflammasome. This review highlights mechanisms regulate resting state, discusses how targeting this can lead novel therapeutic strategies for NLRP3-related diseases.

Язык: Английский

PANoptosis: a potential target of atherosclerotic cardiovascular disease DOI Creative Commons

Xiao Jin,

Yanan Zhu,

Lina Xing

и другие.

APOPTOSIS, Год журнала: 2025, Номер unknown

Опубликована: Апрель 26, 2025

PANoptosis is a newly discovered cell death pathway triggered by the innate immunizer, which in turn promotes assembly of PANoptosome and activates downstream effectors. As special mode, it characterized apoptosis, pyroptosis, necroptosis at same time; therefore, not feasible to inhibit suppressing single pathway. However, active ingredients targeting can effectively PANoptosis.Given importance disease, would be an important therapeutic tool. Previous studies have focused more on infectious diseases cancer, role cardiovascular field has been comprehensively addressed. While ASCVD number one killer diseases, explore new targets determine future research directions. Therefore, this review focuses PANoptosome, molecular mechanism PANoptosis, related mechanisms leading such as myocardial infarction, ischemic cardiomyopathy stroke, order provide perspective for prevention treatment ASCVD.

Язык: Английский

Процитировано

0
Neutrophil extracellular traps aggravate uremic cardiomyopathy by inducing myocardial fibroblast pyroptosis DOI Creative Commons
Ying Xu, Yan Ren,

Wenli Zou

и другие.

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Май 20, 2025

Язык: Английский

Процитировано

0
Deubiquitinases as novel therapeutic targets for diseases DOI Creative Commons

Yali Xian,

Jing Ye,

Yu Tang

и другие.

MedComm, Год журнала: 2024, Номер 5(12)

Опубликована: Дек. 1, 2024

Deubiquitinating enzymes (DUBs) regulate substrate ubiquitination by removing ubiquitin or cleaving within chains, thereby maintaining cellular homeostasis. Approximately 100 DUBs in humans counteract E3 ligases, finely balancing and deubiquitination processes to maintain proteostasis respond various stimuli stresses. Given their role modulating levels of substrates, are increasingly linked human health disease. Here, we review the DUB family, highlighting distinctive structural characteristics chain-type specificities. We show that family members key signaling pathways, such as NF-κB, PI3K/Akt/mTOR, MAPK, play crucial roles tumorigenesis other diseases (neurodegenerative disorders, cardiovascular diseases, inflammatory developmental diseases), making them promising therapeutic targets Our also discusses challenges developing inhibitors underscores critical cancer. This comprehensive analysis enhances our understanding complex biological functions potential.

Язык: Английский

Процитировано

3
NLRP3 Negative Regulation Mechanisms in the Resting State and Its Implications for Therapeutic Development DOI Open Access
Yeji Kim, Sumin Lee, Yong Hwan Park

и другие.

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(16), С. 9018 - 9018

Опубликована: Авг. 20, 2024

The NACHT-, leucine-rich-repeat-, and pyrin domain-containing protein 3 (NLRP3) is a critical intracellular sensor of the innate immune system that detects various pathogen- danger-associated molecular patterns, leading to assembly NLRP3 inflammasome release interleukin (IL) 1β IL-18. However, abnormal activation has been implicated in pathogenesis autoinflammatory diseases such as cryopyrin-associated syndromes (CAPS) common Alzheimer's disease asthma. Recent studies have revealed functions an indirect sensor, similar plant guard system, regulated by binding inhibitory 14-3-3 proteins. Upon activation, transitions its active form. predicted follow regulatory mechanism maintain inactive form cage model, it also acts sensor. Additionally, newly developed inhibitors found inhibit activity stabilizing Most reviews on focused inflammasome. This review highlights mechanisms regulate resting state, discusses how targeting this can lead novel therapeutic strategies for NLRP3-related diseases.

Язык: Английский

Процитировано

2