ArticleMolecular neurodegeneration2023
BACE1 regulates expression of Clusterin in astrocytes for enhancing clearance of β-amyloid peptides.
Article in Molecular neurodegeneration, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- Systematic review and meta-analysis of bulk RNAseq studies in human Alzheimer's disease brain tissue.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Pooled it
- Development of a Novel AAV-Mediated microRNA Gene Therapy for Spatial Suppression of BACE1 to Improve Cognitive Function in Alzheimer's Disease Model Mice.Biomolecules · 2026Article
- Brain-targeted delivery of siRNA via non-viral delivery systems, the therapeutic strategy for Alzheimer's disease-Unveiling challenges and prospects.International journal of pharmaceutics: X · 2026Review
- A Question of Origins: Non-neuronal Sources of Amyloid-β.Neuroscience bulletin · 2026Review
- Extracellular Vesicles in Alzheimer's Disease: Mechanisms, Biomarkers, and Therapeutic Engineering.International journal of molecular sciences · 2026Review
- Nano-magnolol enhances the modulatory effects of magnolol on cognitive performance and BACE1-related biochemical changes in an STZ-induced rat model of Alzheimer's disease.Discover nano · 2026Article
- The rise of astrocytes: are they guardians or troublemakers of the brain disorder?Experimental & molecular medicine · 2026Review
- Nrf2 overexpression reprograms neural stem cell fate: promoting neuronal differentiation and functional recovery post-ischemic stroke via suppression of the ROS/NF-κB axis.Journal of translational medicine · 2026Article
- The complement system in Alzheimer's disease: mechanisms, biomarkers, and therapeutic implications.Frontiers in immunology · 2026Review
- Activity and Heterogeneity of Astrocytes in Neurological Diseases: Molecular Mechanisms and Therapeutic Targets.MedComm · 2025Review
- Deciphering the Structural Biology of GFAP: Connotations of Its Potency in Presaging the Diagnosis for Traumatic Brain Injury and AD.Neurology international · 2025Review
- Clusterin Regulates the Mechanisms of Neuroinflammation and Neuronal Circuit Impairment in Alzheimer's Disease.International journal of molecular sciences · 2025Review
- The Emerging Role of the Molecular Chaperone Clusterin in Parkinson's Disease.International journal of molecular sciences · 2025Review
- Alzheimer's disease protective allele of Clusterin modulates neuronal excitability through lipid-droplet-mediated neuron-glia communication.Molecular neurodegeneration · 2025Article
- Neuronal CCL2 responds to hyperglycaemia and contributes to anxiety disorders in the context of diabetes.Nature metabolism · 2025Article
- P2Y1 receptor in Alzheimer's disease.Neural regeneration research · 2025Article
- Electrophysiology-based screening identifies neuronal HtrA serine peptidase 2 (HTRA2) as a synaptic plasticity regulator participating in tauopathy.Translational psychiatry · 2025Article
- BACE1 at the crossroads of a vicious circle between Alzheimer's disease and diabetes mellitus.Frontiers in dementia · 2025Review
- BMAL1 upregulates STX17 levels to promote autophagosome-lysosome fusion in hippocampal neurons to ameliorate Alzheimer's disease.iScience · 2024Article
- Contribution of amyloid deposition from oligodendrocytes in a mouse model of Alzheimer's disease.Molecular neurodegeneration · 2024Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundAbnormal accumulation of amyloid beta peptide (Aβ) in the brain induces a cascade of pathological changes in Alzheimer's disease (AD), and inhibiting BACE1, which is required for Aβ generation, is therefore being explored for the treatment of AD by reducing Aβ accumulation. As Bace1 knockout mice exhibit increased number of reactive astrocytes and AD brains have reactive astrocytes that surround amyloid plaques, we investigated the role of BACE1 in astrocytes and determined whether BACE1 regulates astrocytic functions.
methodsWe conducted unbiased single cell RNA-seq (scRNA-seq) using purified astrocytes from Bace1 KO mice and wild type control littermates. Similar scRNA-seq was also conducted using AD mice with conditional deletion of Bace1 in the adult stage (5xFAD;Bace1
resultsAmong altered genes, Clusterin (Clu) and Cxcl14 were significantly upregulated and validated by measuring protein levels. Moreover, BACE1 deficiency enhanced both astrocytic Aβ uptake and degradation, and this effect was significantly attenuated by siRNA knockdown of Clu. Mechanistic study suggests that BACE1 deficiency abolishes cleavage of astrocytic insulin receptors (IR), and this may enhance expression of Clu and Cxcl14. Acutely isolated astrocytes from astrocyte-specific knockout of Bace1 mice (Bace1
conclusionTogether, our study suggests that BACE1 in astrocytes regulates expression of Clu and Cxcl14, likely via the control of insulin receptor pathway, and inhibition of astrocytic BACE1 is a potential alternative strategy for enhancing Aβ clearance.
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