MST1/2 in inflammation and immunity

Li, Tongfen; Wen, Yiqiong; Lu, Qiongfen; Hua, Shu; Hou, Yunjiao; Du, Xiaohua; Zheng, Yuanyuan; Sun, Shibo

doi:10.1080/19336918.2023.2276616

Cell Adhesion & Migration

2023

DOI: 10.1080/19336918.2023.2276616

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MST1/2 in inflammation and immunity

Tongfen Li,

Yiqiong Wen,

Qiongfen Lu

et al.

Abstract: The mammalian Sterile 20-like kinase 1/2 (MST1/2) belongs to the serine/threonine (GC) protein kinase superfamily. Collective studies confirm the vital role MST1/2 in inflammation and immunity. MST1/2 is closely related to the progress of inflammation. Generally, MST1/2 aggravates the inflammatory injury through MST1-JNK, MST1-mROS, MST1-Foxo3, and NF-κB pathways, as well as several regulatory factors such as tumor necrosis factor-α (TNF-α), mitochondrial extension factor 1 (MIEF1), and lipopolysaccharide (LPS… Show more

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2024

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Cited by 2 publications

References 99 publications

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Integrative systems neuroimmunology reveals leukocyte-expressing PAX6 as a critical predictor of major depressive disorder

Dias,

Adri,

Nóbile

et al. 2024

Preprint

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Major depressive disorder (MDD) is a complex psychiatric condition with a significant global impact. This study applied a genomic-driven integrative systems neuroimmunology approach to analyze transcriptomic data from 3,114 individuals (1,877 MDD patients and 1,237 controls). The analysis revealed neuroimmunological transcriptomic alterations, indicating cross-talk between the immune and nervous systems in peripheral blood mononuclear cells (PBMCs) and specific brain regions. Among 31 shared genes, NEGR1, PPP6C, SORCS3, and PAX6 emerged as significant predictors of MDD in patients' PBMCs. Notably, PAX6 was also identified as a differentially expressed gene (DEG) in the amygdala, while NEGR1, PPP6C, and SORCS3 showed no significant differential expression in other central nervous system (CNS) regions. Validation by immunophenotyping in a mouse model of chronic stress demonstrated increased PAX6 expression in PBMCs, a gene previously associated with MDD in GWAS studies. Collectively, our findings suggest the existence of shared transcriptomic modules across the brain and immune system, highlighting PAX6 as a potential therapeutic target in MDD.

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Integrative systems neuroimmunology reveals leukocyte-expressing PAX6 as a critical predictor of major depressive disorder

Dias,

Adri,

Nóbile

et al. 2024

Preprint

View full text Add to dashboard Cite

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MST1, a novel therapeutic target for Alzheimer's disease, regulates mitochondrial homeostasis by mediating mitochondrial DNA transcription and PI3K-Akt-ROS pathway.

Wang,

Cui,

Liu

et al. 2024

Preprint

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Background Alzheimer's disease (AD) stands as one of the prevalent irreversible neurodegenerative conditions marked by gradual cognitive deterioration and neuronal loss. The mammalian Ste20-like kinase (MST1)-Hippo pathway is pivotal in regulating cell apoptosis, immune response, mitochondrial function, and oxidative stress. However, the association between MST1 and mitochondrial function in AD remains unknown. Therefore, this study aims to investigate the effect of MST1 on neuronal damage and cognitive impairment by regulating mitochondrial homeostasis in AD. Methods In this study, we selected 4- and 7-month-old 5xFAD mice to simulate the early and middle stages of AD, we assessed cognitive function, detected neuronal damage indicators, and evaluated mitochondrial morphology, dynamics, oxidative stress, ATP, and mitochondrial apoptosis-related indicators. We employed RNA-seq technology to explore potential mechanisms of action. In vitro studies were conducted to investigate the effects of MST1 on the viability and mitochondrial function of SH-SY5Y model cells, aiming to validate the potential molecular mechanisms of MST1. Results Overexpression of MST1 accelerated neuronal degeneration and cognitive deficits, alongside promoting oxidative stress and mitochondrial damage. Similarly, in cell models, MST1 overexpression facilitated apoptosis and mitochondrial dysfunction. Knockdown of MST1 expression and chemical inactivation of MST1 improved cognitive decline, mitochondrial dysfunction while reducing neuronal degeneration. In terms of mechanism, MST1 was found to regulate the transcription of mitochondrial genes, including MT-Nd4L, MT-ATP6, and MT-CO2, by binding to PGC1α. It influenced cellular oxidative stress through the PI3K-Akt-ROS pathway, ultimately disrupting mitochondrial homeostasis and mediating cell damage. Conclusion Overall, our results showed that MST1 primarily regulates mitochondrial DNA transcription levels by interacting with PGC1α and modulates cellular oxidative stress through the PI3K-Akt-ROS pathway, thereby disrupting mitochondrial homeostasis. This discovery can potentially enhance mitochondrial energy metabolism pathways by targeting MST1, thereby offering novel potential therapeutic targets for treating AD.

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MST1/2 in inflammation and immunity

Cited by 2 publications

References 99 publications

Integrative systems neuroimmunology reveals leukocyte-expressing PAX6 as a critical predictor of major depressive disorder

Integrative systems neuroimmunology reveals leukocyte-expressing PAX6 as a critical predictor of major depressive disorder

MST1, a novel therapeutic target for Alzheimer's disease, regulates mitochondrial homeostasis by mediating mitochondrial DNA transcription and PI3K-Akt-ROS pathway.

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