ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2015
microRNA-33 Regulates ApoE Lipidation and Amyloid-β Metabolism in the Brain.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
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Who cites it
80 citing papers in PubMed, 125 citations in OpenAlex.
- Chicoric acid enhanced brain cholesterol efflux and reduced Aβ pathology via LXR-ABCA1 signaling in Alzheimer's models.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Morpho-Functional Characterization and miRNA Profiling of the Retina in the 5xFAD Murine Model of Alzheimer's Disease.Investigative ophthalmology & visual science · 2026Article
- Mechanisms, Mediators, and Pharmacological Approaches Targeting Brain Cholesterol Transport in Alzheimer's Disease.Current pharmaceutical design · 2026Review
- Epigenetics in Alzheimer's disease: from molecular mechanisms to emerging novel biomarkers.Frontiers in aging neuroscience · 2026Review
- MiR-33-5p-opioidergic Signaling Regulates Cognitive Impairment Induced by Bile Duct Ligation in Rats: Ameliorative Role of Naloxone.Brain and behavior · 2025Article
- TREM2 Alleviates Neuroinflammation and Improves Neurogenesis in ApoEMolecular neurobiology · 2025Article
- Therapeutic effects of miR-937-3p by targeting NTN1 expression and regulating apoptosis in an Aβ-induced neuronal cell death.Scientific reports · 2025Article
- Therapeutic potential and microRNA regulating properties of phytochemicals in Alzheimer's disease.Molecular therapy. Nucleic acids · 2025Review
- Deletion of miR-33, a regulator of the ABCA1-APOE pathway, ameliorates neuropathological phenotypes in APP/PS1 mice.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- A new perspective on microRNA-guided gene regulation specificity, and its potential generalization to transcription factors and RNA-binding proteins.Nucleic acids research · 2024Review
- MicroRNA-455-3P as a peripheral biomarker and therapeutic target for mild cognitive impairment and Alzheimer's disease.Ageing research reviews · 2024Review
- Regulatory Roles of MicroRNAs in the Pathogenesis of Metabolic Syndrome.Molecular biotechnology · 2024Review
- The role of ncRNAs in depression.Heliyon · 2024Review
- Mesenchymal Stem Cells from Familial Alzheimer's Patients Express MicroRNA Differently.International journal of molecular sciences · 2024Article
- New insights in lipid metabolism: potential therapeutic targets for the treatment of Alzheimer's disease.Frontiers in neuroscience · 2024Review
- MicroRNA biomarkers as next-generation diagnostic tools for neurodegenerative diseases: a comprehensive review.Frontiers in molecular neuroscience · 2024Review
- Reexamining the Causes and Effects of Cholesterol Deposition in the Brains of Patients with Alzheimer's Disease.Molecular neurobiology · 2023Review
- Roles of Non-Coding RNA in Alzheimer's Disease Pathophysiology.International journal of molecular sciences · 2023Review
- Neuronal ApoE4 in Alzheimer's disease and potential therapeutic targets.Frontiers in aging neuroscience · 2023Review
- Mechanism and Therapeutic Prospect of miRNAs in Neurodegenerative Diseases.Behavioural neurology · 2023Review
20 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 7 institutions in 2 countries.
Funding
Abstract
Dysregulation of amyloid-β (Aβ) metabolism is critical for Alzheimer's disease (AD) pathogenesis. Mounting evidence suggests that apolipoprotein E (ApoE) is involved in Aβ metabolism. ATP-binding cassette transporter A1 (ABCA1) is a key regulator of ApoE lipidation, which affects Aβ levels. Therefore, identifying regulatory mechanisms of ABCA1 expression in the brain may provide new therapeutic targets for AD. Here, we demonstrate that microRNA-33 (miR-33) regulates ABCA1 and Aβ levels in the brain. Overexpression of miR-33 impaired cellular cholesterol efflux and dramatically increased extracellular Aβ levels by promoting Aβ secretion and impairing Aβ clearance in neural cells. In contrast, genetic deletion of mir-33 in mice dramatically increased ABCA1 levels and ApoE lipidation, but it decreased endogenous Aβ levels in cortex. Most importantly, pharmacological inhibition of miR-33 via antisense oligonucleotide specifically in the brain markedly decreased Aβ levels in cortex of APP/PS1 mice, representing a potential therapeutic strategy for AD. SIGNIFICANCE STATEMENT: Brain lipid metabolism, in particular Apolipoprotein E (ApoE) lipidation, is critical to Aβ metabolism and Alzheimer's disease (AD). Brain lipid metabolism is largely separated from the periphery due to blood-brain barrier and different repertoire of lipoproteins. Therefore, identifying the novel regulatory mechanism of brain lipid metabolism may provide a new therapeutic strategy for AD. Although there have been studies on brain lipid metabolism, its regulation, in particular by microRNAs, is relatively unknown. Here, we demonstrate that inhibition of microRNA-33 increases lipidation of brain ApoE and reduces Aβ levels by inducing ABCA1. We provide a unique approach for AD therapeutics to increase ApoE lipidation and reduce Aβ levels via pharmacological inhibition of microRNA in vivo.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.