ArticleApoptosis : an international journal on programmed cell death2024
MST1 selective inhibitor Xmu-mp-1 ameliorates neuropathological changes in a rat model of sporadic Alzheimer's Disease by modulating Hippo-Wnt signaling crosstalk.
Article in Apoptosis : an international journal on programmed cell death, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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8 citing papers in PubMed.
- Xmu-mp-1 attenuates streptozotocin-induced neurotoxicity in SH-SY5Y cells: potential role of Hippo pathway modulation.Molecular biology reports · 2026Article
- Review
- Mammalian Sterile 20-Like Kinase 2 Knockdown Alleviates Neuropathic Pain in Rats by Mitochondrial Protection.Molecular neurobiology · 2025Article
- Tead1a Initiates Transcriptional Priming Through the TEAD1a/YAP-Notch1-Spi1/Cebpα Axis to Promote Neutrophil Fate.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The Hippo signaling pathway as a therapeutic target in Alzheimer's disease.Molecular neurodegeneration · 2025Review
- Tanshinone IIA attenuates hepatic stellate cell activation, oxidative stress, and liver fibrosis by inhibiting YAP signaling.European journal of histochemistry : EJH · 2025Article
- Wnt signaling pathways in biology and disease: mechanisms and therapeutic advances.Signal transduction and targeted therapy · 2025Review
- 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 · 2024Article
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Abstract
Alzheimer's disease (AD), the most prevalent form of dementia, is characterized by progressive cognitive impairment accompanied by aberrant neuronal apoptosis. Reports suggest that the pro-apoptotic mammalian set20-like kinase 1/2 (MST1/2) instigates neuronal apoptosis via activating the Hippo signaling pathway under various stress conditions, including AD. However, whether inhibiting MST1/2 has any therapeutic benefits in AD remains unknown. Thus, we tested the therapeutic effects of intervening MST1/2 activation via the pharmacological inhibitor Xmu-mp-1 in a sporadic AD rat model. Sporadic AD was established in adult rats by intracerebroventricular streptozotocin (ICV-STZ) injection (3 mg/kg body weight). Xmu-mp-1 (0.5 mg/kg/body weight) was administered once every 48 h for two weeks, and Donepezil (5 mg/kg body weight) was used as a reference standard drug. The therapeutic effects of Xmu-mp-1 on ICV-STZ rats were determined through various behavioral, biochemical, histopathological, and molecular tests. At the behavioral level, Xmu-mp-1 improved cognitive deficits in sporadic AD rats. Further, Xmu-mp-1 treatment reduced STZ-associated tau phosphorylation, amyloid-beta deposition, oxidative stress, neurotoxicity, neuroinflammation, synaptic dysfunction, neuronal apoptosis, and neurodegeneration. Mechanistically, Xmu-mp-1 exerted these neuroprotective actions by inactivating the Hippo signaling while potentiating the Wnt/β-Catenin signaling in the AD rats. Together, the results of the present study provide compelling support that Xmu-mp-1 negated the neuronal dysregulation in the rat model of sporadic AD. Therefore, inhibiting MST/Hippo signaling and modulating its crosstalk with the Wnt/β-Catenin pathway can be a promising alternative treatment strategy against AD pathology. This is the first study providing novel mechanistic insights into the therapeutic use of Xmu-mp-1 in sporadic AD.
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