ArticleMolecular psychiatry2019
Novel upregulation of amyloid-β precursor protein (APP) by microRNA-346 via targeting of APP mRNA 5'-untranslated region: Implications in Alzheimer's disease.
Article in Molecular psychiatry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers, 1 of them a synthesis that pooled it.
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Who cites it
90 citing papers in PubMed, 1 synthesis or guideline pooled it, 141 citations in OpenAlex.
- Pooled it
- miR-149 Promotes Apoptosis of Ovarian Granulosa Cells Through Inducing Caspase 8 Expression.Animals : an open access journal from MDPI · 2026Article
- The role of MicroRNAs in Alzheimer's disease: from pathogenesis to therapeutic potential.Molecular biology reports · 2026Review
- Reexamining the Role of Amyloid β Clearance from the Brain: Exporting Labile Iron from the Interstitial Fluid Performs a Protective Function.International journal of molecular sciences · 2026Review
- Review
- MiRNA-Mediated Regulation of S100B: A Review.NeuroSci · 2025Review
- MicroRNA-153-3p targets repressor element 1-silencing transcription factor (REST) and neuronal differentiation: Implications for Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- A human neuron alzheimer's disease model reveals barriers to senolytic translatability.Alzheimer's research & therapy · 2025Article
- Therapeutic effects of miR-937-3p by targeting NTN1 expression and regulating apoptosis in an Aβ-induced neuronal cell death.Scientific reports · 2025Article
- Systematic Identification of Mitochondrial Signatures in Alzheimer's Disease and Inflammatory Bowel Disease.Molecular neurobiology · 2025Article
- Targeting Regulatory Noncoding RNAs in Human Cancer: The State of the Art in Clinical Trials.Pharmaceutics · 2025Review
- The interaction between ΔNp63α and TAp63α, mediated by miR-205-5p, inhibits the migration of lung adenocarcinoma cells.Scientific reports · 2025Article
- Therapeutic potential and microRNA regulating properties of phytochemicals in Alzheimer's disease.Molecular therapy. Nucleic acids · 2025Review
- Direct and indirect role of non-coding RNAs in company with amyloid and tau protein in promoting neuroinflammation in post-ischemic brain neurodegeneration.Frontiers in cellular neuroscience · 2025Review
- Iron responsive elements mRNA regulate Alzheimer's amyloid precursor protein translation through iron sensing.Frontiers in aging neuroscience · 2025Review
- Sodium Thiosulfate: An Innovative Multi-Target Repurposed Treatment Strategy for Late-Onset Alzheimer's Disease.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Unveiling the multifaceted pathogenesis and therapeutic drugs of Alzheimer's disease: A comprehensive review.Heliyon · 2024Review
- Insights into the Role of microRNAs as Clinical Tools for Diagnosis, Prognosis, and as Therapeutic Targets in Alzheimer's Disease.International journal of molecular sciences · 2024Review
- MicroRNA-455-3P as a peripheral biomarker and therapeutic target for mild cognitive impairment and Alzheimer's disease.Ageing research reviews · 2024Review
- Alterations of mRNAs and Non-coding RNAs Associated with Neuroinflammation in Alzheimer's Disease.Molecular neurobiology · 2024Review
30 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
In addition to the devastating symptoms of dementia, Alzheimer's disease (AD) is characterized by accumulation of the processing products of the amyloid-β (Aβ) peptide precursor protein (APP). APP's non-pathogenic functions include regulating intracellular iron (Fe) homeostasis. MicroRNAs are small (~ 20 nucleotides) RNA species that instill specificity to the RNA-induced silencing complex (RISC). In most cases, RISC inhibits mRNA translation through the 3'-untranslated region (UTR) sequence. By contrast, we report a novel activity of miR-346: specifically, that it targets the APP mRNA 5'-UTR to upregulate APP translation and Aβ production. This upregulation is reduced but not eliminated by knockdown of argonaute 2. The target site for miR-346 overlaps with active sites for an iron-responsive element (IRE) and an interleukin-1 (IL-1) acute box element. IREs interact with iron response protein1 (IRP1), an iron-dependent translational repressor. In primary human brain cultures, miR-346 activity required chelation of Fe. In addition, miR-346 levels are altered in late-Braak stage AD. Thus, miR-346 plays a role in upregulation of APP in the CNS and participates in maintaining APP regulation of Fe, which is disrupted in late stages of AD. Further work will be necessary to integrate other metals, and IL-1 into the Fe-miR-346 activity network. We, thus, propose a "FeAR" (Fe, APP, RNA) nexus in the APP 5'-UTR that includes an overlapping miR-346-binding site and the APP IRE. When a "healthy FeAR" exists, activities of miR-346 and IRP/Fe interact to maintain APP homeostasis. Disruption of an element that targets the FeAR nexus would lead to pathogenic disruption of APP translation and protein production.
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