ArticleThe Journal of biological chemistry2010
Differential regulation of interleukin-1 receptor-associated kinase-1 (IRAK-1) and IRAK-2 by microRNA-146a and NF-kappaB in stressed human astroglial cells and in Alzheimer disease.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 171 papers, 4 of them syntheses that pooled it.
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Who cites it
171 citing papers in PubMed, 4 syntheses or guidelines pooled it, 266 citations in OpenAlex.
- The Role of Exosome-miRNA as Biomarkers of Alzheimer's Disease: A Systematic Review of Case-Control and Longitudinal Studies.Actas espanolas de psiquiatria · 2026Pooled it
- A Systematic Review of MicroRNA Expression as Biomarker of Late-Onset Alzheimer's Disease.Molecular neurobiology · 2019Pooled it
- Systematic Review of miRNA as Biomarkers in Alzheimer's Disease.Molecular neurobiology · 2019Pooled it
- Role of microRNAs in the Therapeutic Effects of Curcumin in Non-Cancer Diseases.Molecular diagnosis & therapy · 2016Pooled it
- NF-κB across the Alzheimer disease spectrum: Context-dependent protective and pathogenic roles.IBRO neuroscience reports · 2026Review
- MicroRNA and Alzheimer's disease: Diagnostic biomarkers and potential therapeutic targets.Neural regeneration research · 2026Article
- Down-Regulation of Acyloxyacyl Hydrolase Expression in Alzheimer's Disease Impairs LPS Detoxification and Contributes to Brain Pro-Inflammatory Signaling.Molecules (Basel, Switzerland) · 2026Article
- Uncovering the dynamics of extracellular vesicle microRNA trafficking in multiple sclerosis: delivery, diversion and retention.Extracellular vesicles and circulating nucleic acids · 2026Review
- MicroRNAs in neurodegenerative diseases: from molecular mechanisms to clinical biomarkers, detection methods and therapeutic strategies-advances and challenges.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025Review
- Exosomal miR-146a-3p modulates neural stem cell fate through UCHL1 downregulation in spinal cord injury: implications for neuroregeneration.Acta biochimica et biophysica Sinica · 2025Article
- Nutritional strategies against dementia in rural populations.Frontiers in nutrition · 2025Review
- Shared and distinct changes in the molecular cargo of extracellular vesicles in different neurodegenerative diseases.Cellular and molecular life sciences : CMLS · 2024Review
- The Role of Non-Coding RNAs in Mitochondrial Dysfunction of Alzheimer's Disease.Journal of molecular neuroscience : MN · 2024Review
- Transcriptional profiling in microglia across physiological and pathological states identifies a transcriptional module associated with neurodegeneration.Communications biology · 2024Article
- Spinal Cord Injury: From MicroRNAs to Exosomal MicroRNAs.Molecular neurobiology · 2024Review
- Can exercise benefits be harnessed with drugs? A new way to combat neurodegenerative diseases by boosting neurogenesis.Translational neurodegeneration · 2024Review
- Alzheimer's disease-induced phagocytic microglia express a specific profile of coding and non-coding RNAs.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Mesenchymal Stem Cells from Familial Alzheimer's Patients Express MicroRNA Differently.International journal of molecular sciences · 2024Article
- A microRNA diagnostic biomarker for amyotrophic lateral sclerosis.Brain communications · 2024Article
- MicroRNA biomarkers as next-generation diagnostic tools for neurodegenerative diseases: a comprehensive review.Frontiers in molecular neuroscience · 2024Review
111 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Specific microRNAs (miRNAs), small non-coding RNAs that support homeostatic gene expression, are significantly altered in abundance in human neurological disorders. In monocytes, increased expression of an NF-κB-regulated miRNA-146a down-regulates expression of the interleukin-1 receptor-associated kinase-1 (IRAK-1), an essential component of Toll-like/IL-1 receptor signaling. Here we extend those observations to the hippocampus and neocortex of Alzheimer disease (AD) brain and to stressed human astroglial (HAG) cells in primary culture. In 66 control and AD samples we note a significant up-regulation of miRNA-146a coupled to down-regulation of IRAK-1 and a compensatory up-regulation of IRAK-2. Using miRNA-146a-, IRAK-1-, or IRAK-2 promoter-luciferase reporter constructs, we observe decreases in IRAK-1 and increases in miRNA-146a and IRAK-2 expression in interleukin-1β (IL-1β) and amyloid-β-42 (Aβ42) peptide-stressed HAG cells. NF-κB-mediated transcriptional control of human IRAK-2 was localized to between -119 and +12 bp of the immediate IRAK-2 promoter. The NF-κB inhibitors curcumin, pyrrolidine dithiocarbamate or CAY10512 abrogated both IRAK-2 and miRNA-146a expression, whereas IRAK-1 was up-regulated. Incubation of a protected antisense miRNA-146a was found to inhibit miRNA-146a and restore IRAK-1, whereas IRAK-2 remained unaffected. These data suggest a significantly independent regulation of IRAK-1 and IRAK-2 in AD and in IL-1β+Aβ42 peptide-stressed HAG cells and that an inducible, NF-κB-sensitive, miRNA-146a-mediated down-regulation of IRAK-1 coupled to an NF-κB-induced up-regulation of IRAK-2 expression drives an extensively sustained inflammatory response. The interactive signaling of NF-κB and miRNA-146a further illustrate interplay between inducible transcription factors and pro-inflammatory miRNAs that regulate brain IRAK expression. The combinatorial use of NF-κB inhibitors with miRNA-146a or antisense miRNA-146a may have potential as a bi-pronged therapeutic strategy directed against IRAK-2-driven pathogenic signaling.
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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.