ArticleJournal of translational medicine2024
SIRT6 prevent chronic cerebral hypoperfusion induced cognitive impairment by remodeling mitochondrial dynamics in a STAT5-PGAM5-Drp1 dependent manner.
Article in Journal of translational medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Oxidative stress in neurodegeneration: from a simple insult to a dynamic regulator.Redox report : communications in free radical research · 2026Review
- Mitochondrial Fusion and Fission in Age-Related Cardio-Cerebral Diseases: Mechanisms and Interventions.Aging cell · 2026Review
- Neuromodulation Techniques in Chronic Cerebral Hypoperfusion: Mechanisms and Therapeutic Advances.CNS neuroscience & therapeutics · 2026Review
- A review of animal models of vascular dementia.Molecular biology reports · 2026Review
- Inflammation-targeted single-atom nanozymes drive microglial depolarization and inhibit ferroptosis via Sirt-6-xCT-GPX4 axis to attenuate early brain injury following subarachnoid hemorrhage.Materials today. Bio · 2026Article
- Article
- Endothelial senescence of the vertebral artery in the context of cervical degeneration: biomechanically driven remodeling of the hemodynamic environment.Frontiers in cell and developmental biology · 2026Review
- Sirtuin 6 mitigates thoracic aortic aneurysm progression via maintenance of mitochondria homeostasis in vascular smooth muscle cells.Acta pharmacologica Sinica · 2026Article
- Edaravone dexborneol alleviates pericyte-mediated fibrosis depositing extracellular matrix through TGF-β1/IL-11 in cerebral small vessel disease.Journal of translational medicine · 2025Article
- The therapeutic effects and mechanisms of glucagon-like peptide-1 receptor agonists in neurocognitive disorders.Therapeutic advances in neurological disorders · 2025Review
- Integrated bioinformatics analysis and biological experiments to identify key immune genes in vascular dementia.Frontiers in immunology · 2025Article
- Multi-omics exploration of chaperone-mediated immune-proteostasis crosstalk in vascular dementia and identification of diagnostic biomarkers.Frontiers in immunology · 2025Article
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Authors and funding
10 authors.
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Abstract
Vascular dementia (VaD) is a prevalent form of dementia resulting from chronic cerebral hypoperfusion (CCH). However, the pathogenic mechanisms of VaD and corresponding therapeutic strategies are not well understood. Sirtuin 6 (SIRT6) has been implicated in various biological processes, including cellular metabolism, DNA repair, redox homeostasis, and aging. Nevertheless, its functional relevance in VaD remains unexplored. In this study, we utilized a bilateral common carotid artery stenosis (BCAS) mouse model of VaD to investigate the role of SIRT6. We detected a significant decrease in neuronal SIRT6 protein expression following CCH. Intriguingly, neuron-specific ablation of Sirt6 in mice exacerbated neuronal damage and cognitive deficits after CCH. Conversely, treatment with MDL-800, an agonist of SIRT6, effectively mitigated neuronal loss and facilitated neurological recovery. Mechanistically, SIRT6 inhibited excessive mitochondrial fission by suppressing the CCH-induced STAT5-PGAM5-Drp1 signaling cascade. Additionally, the gene expression of monocyte SIRT6 in patients with asymptomatic carotid stenosis showed a correlation with cognitive outcomes, suggesting translational implications in human subjects. Our findings provide the first evidence that SIRT6 prevents cognitive impairment induced by CCH, and mechanistically, this protection is achieved through the remodeling of mitochondrial dynamics in a STAT5-PGAM5-Drp1-dependent manner.
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