ArticleActa neuropathologica communications2021
STAT3 inhibitor mitigates cerebral amyloid angiopathy and parenchymal amyloid plaques while improving cognitive functions and brain networks.
Article in Acta neuropathologica communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 50 citations in OpenAlex.
- STAT3 Inhibitor Suppresses CCL2-dependent Recruitment and M2 Polarization of Tumor-associated Macrophages to Enhance Antitumor Immunity in Ovarian Cancer.Applied biochemistry and biotechnology · 2026Article
- Microglial Deubiquitinase OTUD7B Stabilizes STAT3 to Promote Neuroinflammation and Cognitive Decline in Alzheimer's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Cyclosporine A Modulates Neuroinflammation-Related Gene Expression Associated with Alzheimer's Disease in SH-SY5Y Neuronal Cell Line: Is Cyclosporine A Beneficial/Detrimental?Biochemical genetics · 2026Article
- Neuroinflammation and Secretase Regulation in Alzheimer's Disease: From Molecular Cross-Talk to Multi-Target Therapeutics.International journal of molecular sciences · 2026Review
- Generation of hiPSC-Derived Brain Microvascular Endothelial Cells Using Directed Differentiation and Transcriptional Reprogramming.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- Psoralen regulates bone degenerative diseases by inhibiting APP phosphorylation to regulate MAPK and STAT3 signaling.American journal of translational research · 2026Article
- Post-Translational Modifications Distinguish Amyloid-β Isoforms in Cerebral Amyloid Angiopathy and Alzheimer's Disease.Journal of neurochemistry · 2025Article
- Proinflammatory transcriptomic and kinomic alterations in astrocytes derived from patients with familial Alzheimer's disease.Brain, behavior, & immunity - health · 2025Article
- Alzheimer's disease and age-related macular degeneration: Shared and distinct immune mechanisms.Immunity · 2025Review
- The NeuroProtect Formula: A Preventive Approach to AD Targeting the HIF-1/PI3K-AKT Signaling Pathway Evaluated throughCombinatorial chemistry & high throughput screening · 2025Article
- Neuroprotective Effects of STAT3 Inhibitor on Hydrogen Peroxide-Induced Neuronal Cell Death via the ERK/CREB Signaling Pathway.Neurochemical research · 2024Article
- Development and Validation of a Prechiasmatic Mouse Model of Subarachnoid Hemorrhage to Measure Long-Term Cognitive Deficits.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Exploring the mechanism of sunflower seed oil against Alzheimer's disease through experimental and network pharmacology studies.Indian journal of pharmacology · 2024Article
- Diffusion imaging genomics provides novel insight into early mechanisms of cerebral small vessel disease.Molecular psychiatry · 2024Article
- Protein Kinase C-Delta Mediates Cell Cycle Reentry and Apoptosis Induced by Amyloid-Beta Peptide in Post-Mitotic Cortical Neurons.International journal of molecular sciences · 2024Article
- PPARγ activation ameliorates cognitive impairment and chronic microglial activation in the aftermath of r-mTBI.Journal of neuroinflammation · 2024Article
- Development and validation of prechiasmatic mouse model of subarachnoid hemorrhage to measure long-term neurobehavioral impairment.Research square · 2024Article
- Interleukin-22 Contributes to Blood-Brain Barrier Disruption via STAT3/VEGFA Activation inACS infectious diseases · 2024Article
- Article
- Emerging functions and therapeutic targets of IL-38 in central nervous system diseases.CNS neuroscience & therapeutics · 2024Review
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Previous reports indicate a potential role for signal transducer and activator of transcription 3 (STAT3) in amyloid-β (Aβ) processing and neuritic plaque pathogenesis. In the present study, the impact of STAT3 inhibition on cognition, cerebrovascular function, amyloid pathology, oxidative stress, and neuroinflammation was studied using in vitro and in vivo models of Alzheimer's disease (AD)-related pathology. For in vitro experiments, human brain vascular smooth muscle cells (HBVSMC) and human brain microvascular endothelial cells (HBMEC) were used, and these cultured cells were exposed to Aβ peptides followed by measurement of activated forms of STAT3 expression and reactive oxygen species (ROS) generation. Further, 6 months old 5XFAD/APOE4 (5XE4) mice and age-matched negative littermates were used for in vivo experiments. These mice were treated with STAT3 specific inhibitor, LLL-12 for 2 months followed by neurobehavioral and histopathological assessment. In vitro experiments showed exposure of cerebrovascular cells to Aβ peptides upregulated activated forms of STAT3 and produced STAT3-mediated vascular oxidative stress. 5XE4 mice treated with the STAT3-specific inhibitor (LLL-12) improved cognitive functions and functional connectivity and augmented cerebral blood flow. These functional improvements were associated with a reduction in neuritic plaques, cerebral amyloid angiopathy (CAA), oxidative stress, and neuroinflammation. Reduction in amyloid precursor protein (APP) processing and attenuation of oxidative modification of lipoprotein receptor related protein-1 (LRP-1) were identified as potential underlying mechanisms. These results demonstrate the broad impact of STAT3 on cognitive functions, parenchymal and vascular amyloid pathology and highlight the therapeutic potential of STAT3 specific inhibition for treatment of AD and CAA.
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