ArticleAging cell2016
Amyloid β-induced astrogliosis is mediated by β1-integrin via NADPH oxidase 2 in Alzheimer's disease.
Article in Aging cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 81 citations in OpenAlex.
- Article
- Human brain and organoid transcriptomes reveal key receptor tyrosine kinase pathways and genetic signatures in Alzheimer's disease.Experimental & molecular medicine · 2026Article
- Plasma GFAP as a mediator and moderator of Aβ, tau, and neurodegeneration in Alzheimer's disease.NPJ dementia · 2026Article
- Beyond Radical Scavengers: Focus on NADPH Oxidases (NOX) Inhibitors as New Agents for Antioxidant Therapy in Alzheimer's Disease.Antioxidants (Basel, Switzerland) · 2025Review
- The Reciprocal Relationship Between Cell Adhesion Molecules and Reactive Oxygen Species.Cells · 2025Review
- Article
- Mechanistic Role of Astrocytic Rac1 Protein in Alzheimer's Disease.Aging and disease · 2025Review
- Design of Benzyl-triazolopyrimidine-Based NADPH Oxidase Inhibitors Leads to the Discovery of a Potent Dual Covalent NOX2/MAOB Inhibitor.Journal of medicinal chemistry · 2025Article
- The Dual Role of Amyloid Beta-Peptide in Oxidative Stress and Inflammation: Unveiling Their Connections in Alzheimer's Disease Etiopathology.Antioxidants (Basel, Switzerland) · 2024Review
- Hybrid Amyloid Quantum Dot Nano-Bio Assemblies to Probe Neuroinflammatory Damage.ACS chemical neuroscience · 2024Article
- Identification of key proteins in early-onset Alzheimer's disease based on WGCNA.Frontiers in aging neuroscience · 2024Article
- Associations of amyloid-β oligomers and plaques with neuropathology in theBrain communications · 2024Article
- NADPH Oxidases: From Molecular Mechanisms to Current Inhibitors.Journal of medicinal chemistry · 2023Review
- Amyloid βCells · 2023Article
- Functional Correlates of Microglial and Astrocytic Activity in Symptomatic Sporadic Alzheimer's Disease: A CSF/Biomedicines · 2023Article
- Targeting integrin pathways: mechanisms and advances in therapy.Signal transduction and targeted therapy · 2023Review
- Global trends and prospects about synaptic plasticity in Alzheimer's disease: a bibliometric analysis.Frontiers in aging neuroscience · 2023Review
- Plasma Glial Fibrillary Acidic Protein Is Associated with 18F-SMBT-1 PET: Two Putative Astrocyte Reactivity Biomarkers for Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2023Article
- Aβ42 oligomer-specific antibody ALZ-201 reduces the neurotoxicity of Alzheimer's disease brain extracts.Alzheimer's research & therapy · 2022Article
- Inflammation context in Alzheimer's disease, a relationship intricate to define.Biological research · 2022Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Astrogliosis is a hallmark of Alzheimer's disease (AD) and may constitute a primary pathogenic component of that disorder. Elucidation of signaling cascades inducing astrogliosis should help characterizing the function of astrocytes and identifying novel molecular targets to modulate AD progression. Here, we describe a novel mechanism by which soluble amyloid-β modulates β1-integrin activity and triggers NADPH oxidase (NOX)-dependent astrogliosis in vitro and in vivo. Amyloid-β oligomers activate a PI3K/classical PKC/Rac1/NOX pathway which is initiated by β1-integrin in cultured astrocytes. This mechanism promotes β1-integrin maturation, upregulation of NOX2 and of the glial fibrillary acidic protein (GFAP) in astrocytes in vitro and in hippocampal astrocytes in vivo. Notably, immunochemical analysis of the hippocampi of a triple-transgenic AD mouse model shows increased levels of GFAP, NOX2, and β1-integrin in reactive astrocytes which correlates with the amyloid β-oligomer load. Finally, analysis of these proteins in postmortem frontal cortex from different stages of AD (II to V/VI) and matched controls confirmed elevated expression of NOX2 and β1-integrin in that cortical region and specifically in reactive astrocytes, which was most prominent at advanced AD stages. Importantly, protein levels of NOX2 and β1-integrin were significantly associated with increased amyloid-β load in human samples. These data strongly suggest that astrogliosis in AD is caused by direct interaction of amyloid β oligomers with β1-integrin which in turn leads to enhancing β1-integrin and NOX2 activity via NOX-dependent mechanisms. These observations may be relevant to AD pathophysiology.
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