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

Journal of Translational Medicine, Год журнала: 2024, Номер 22(1)

Опубликована: Ноя. 22, 2024

Alzheimer's disease (AD) is a prevalent irreversible neurodegenerative condition marked by gradual cognitive deterioration and neuronal loss. The mammalian Ste20-like kinase (MST1)–Hippo pathway pivotal in regulating cell apoptosis, immune response, mitochondrial function, oxidative stress. However, the association between MST1 function AD remains unknown. Therefore, this study investigates effect of on damage impairment homeostasis AD. In study, 4- 7-month-old 5xFAD mice were selected to simulate early middle stages AD, respectively; age-matched wild-type served as controls for comparative analysis. Adeno-associated virus (AAV) was injected into hippocampus mice. Four weeks post-injection, indicators, morphology, dynamics, stress, ATP, apoptosis-related indicators evaluated. Additionally, RNA-sequencing performed hippocampal tissue MST1-knockdown Subsequently, Gene Ontology (GO) enrichment Kyoto Encyclopedia Genes Genomes (KEGG) analyses differentially expressed genes elucidate potential mechanism MST1. vitro studies investigate effects SH-SY5Y model viability validate underlying molecular mechanisms. overexpression accelerated degeneration deficits vivo while promoting stress damage. Similarly, vitro, facilitated apoptosis dysfunction. knockdown chemical inactivation reduced decline, dysfunction, degeneration. Mechanistically, regulated transcription genes, including MT-ND4L, MT-ATP6, MT-CO2, binding PGC1α. Moreover, influenced cellular through PI3K-Akt-ROS pathway, ultimately disrupting mediating Cumulatively, these results suggest that primarily regulates DNA levels interacting with PGC1α modulates homeostasis. This discovery can be exploited potentially enhance energy metabolism pathways targeting MST1, offering novel therapeutic targets treating

Язык: Английский

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Diagnosis of neuromuscular disorder

Elsevier eBooks, Год журнала: 2025, Номер unknown, С. 225 - 240

Опубликована: Янв. 1, 2025

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Diagnosis of liver disorder

Elsevier eBooks, Год журнала: 2025, Номер unknown, С. 199 - 224

Опубликована: Янв. 1, 2025

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Leveraging endophytic fungi and multiomics integration for targeted drug discovery

Elsevier eBooks, Год журнала: 2025, Номер unknown, С. 277 - 293

Опубликована: Янв. 1, 2025

Язык: Английский

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Mitochondrial disorders: Emerging paradigms and the road ahead to personalized medicine

Neurotherapeutics, Год журнала: 2024, Номер 21(1), С. e00332 - e00332

Опубликована: Янв. 1, 2024

Язык: Английский

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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.

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Июль 22, 2024

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, oxidative stress. However, association between MST1 function AD remains unknown. Therefore, this study aims to investigate effect on damage impairment homeostasis AD. Methods In study, we selected 4- 7-month-old 5xFAD mice simulate early middle stages AD, assessed detected indicators, evaluated morphology, dynamics, stress, ATP, apoptosis-related indicators. We employed RNA-seq technology explore potential mechanisms action. vitro studies were conducted effects viability SH-SY5Y model cells, aiming validate molecular MST1. Results Overexpression accelerated degeneration deficits, alongside promoting stress damage. Similarly, models, overexpression facilitated apoptosis dysfunction. Knockdown expression chemical inactivation improved decline, dysfunction while reducing degeneration. terms mechanism, was found regulate transcription genes, including MT-Nd4L, MT-ATP6, MT-CO2, binding PGC1α. It influenced cellular through PI3K-Akt-ROS pathway, ultimately disrupting mediating Conclusion Overall, our results showed that primarily regulates DNA levels interacting with PGC1α modulates thereby homeostasis. This discovery can potentially enhance energy metabolism pathways targeting MST1, offering novel therapeutic targets for treating

Язык: Английский

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Functional Genomics and Human Diseases

Опубликована: Янв. 1, 2024

Язык: Английский

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Mitochondrial Diseases

Elsevier eBooks, Год журнала: 2024, Номер unknown, С. 596 - 606.e8

Опубликована: Янв. 1, 2024

Язык: Английский

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