{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T18:07:08Z","timestamp":1789150028721,"version":"build-2803163510"},"reference-count":106,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Nebraska Medical Center Startup Fund"},{"id":[{"id":"https:\/\/ror.org\/00thqtb16","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Department of Anesthesiology Lieberman Research Award Fund"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Brain aging is accompanied by changes in RNA homeostasis, intercellular communication, and stress responses that increase vulnerability to neurodegenerative diseases. The neuronal protein HuD (ELAVL4) and the broadly expressed HuR (ELAVL1) regulate RNA stability, translation, localization, and selected microRNA (miRNA) activities. Recent studies further show that HuD can promote export of let-7a and miR-125b during differentiation of PC12 cells, whereas HuR can bind selected miRNAs and engage endosomal export or intracellular buffering mechanisms in other cellular contexts. These observations support an emerging ELAVL\u2013miRNA\u2013extracellular vesicle (EV) framework. They do not yet establish an integrated HuD\/HuR-dependent neuron\u2013glia pathway in aging human brain or Alzheimer\u2019s disease (AD). We therefore distinguish direct, model-specific findings from hypotheses that age-, amyloid-, or inflammation-associated changes in ELAVL abundance, localization, or RNA binding could redistribute miRNAs between intracellular pools and EVs. Testing this framework in primary human neural cells, induced pluripotent stem cell-derived systems, organoids, and in vivo models may identify context-specific mechanisms and therapeutic opportunities.<\/jats:p>","DOI":"10.3390\/cells15181649","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T17:14:59Z","timestamp":1789146899000},"page":"1649","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["ELAVL Proteins, miRNA Fate, and Extracellular RNA Communication in Brain Aging and Neurodegeneration"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6520-4846","authenticated-orcid":false,"given":"Kamalika","family":"Mukherjee","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9697-3824","authenticated-orcid":false,"given":"Suvendra N.","family":"Bhattacharyya","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/15476286.2025.2471133","article-title":"ELAV\/Hu RNA-binding protein family: Key regulators in neurological disorders, cancer, and other diseases","volume":"22","author":"Wutikeli","year":"2025","journal-title":"RNA Biol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Silvestri, B., Mochi, M., Garone, M.G., and Rosa, A. (2022). Emerging Roles for the RNA-Binding Protein HuD (ELAVL4) in Nervous System Diseases. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232314606"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1111\/jnc.12266","article-title":"A HuD-ZBP1 ribonucleoprotein complex localizes GAP-43 mRNA into axons through its 3\u2032 untranslated region AU-rich regulatory element","volume":"126","author":"Yoo","year":"2013","journal-title":"J. Neurochem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.brainres.2017.01.019","article-title":"HuD-mediated distinct BDNF regulatory pathways promote regeneration after nerve injury","volume":"1659","author":"Sanna","year":"2017","journal-title":"Brain Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1002\/jnr.21099","article-title":"Dynamic association with polysomes during P19 neuronal differentiation and an untranslated-region-dependent translation regulation of the tau mRNA by the tau mRNA-associated proteins IMP1, HuD, and G3BP1","volume":"85","author":"Atlas","year":"2007","journal-title":"J. Neurosci. Res."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Sena, R.M., Twiss, J.L., Gardiner, A.S., Dell\u2019Orco, M., Linsenbardt, D.N., and Perrone-Bizzozero, N.I. (2021). The RNA-Binding Protein HuD Regulates Alternative Splicing and Alternative Polyadenylation in the Mouse Neocortex. Molecules, 26.","DOI":"10.3390\/molecules26102836"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"10337","DOI":"10.1073\/pnas.1104928108","article-title":"Interaction of survival of motor neuron (SMN) and HuD proteins with mRNA cpg15 rescues motor neuron axonal deficits","volume":"108","author":"Akten","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"11559","DOI":"10.1523\/JNEUROSCI.1528-17.2017","article-title":"HuD and the Survival Motor Neuron Protein Interact in Motoneurons and Are Essential for Motoneuron Development, Function, and mRNA Regulation","volume":"37","author":"Duy","year":"2017","journal-title":"J. Neurosci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1016\/j.molcel.2012.01.016","article-title":"RNA-binding protein HuD controls insulin translation","volume":"45","author":"Lee","year":"2012","journal-title":"Mol. Cell"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Dell\u2019Orco, M., Elyaderani, A., Vannan, A., Sekar, S., Powell, G., Liang, W.S., Neisewander, J.L., and Perrone-Bizzozero, N.I. (2021). HuD Regulates mRNA-circRNA-miRNA Networks in the Mouse Striatum Linked to Neuronal Development and Drug Addiction. Biology, 10.","DOI":"10.3390\/biology10090939"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.expneurol.2015.02.036","article-title":"Spinal RyR2 pathway regulated by the RNA-binding protein HuD induces pain hypersensitivity in antiretroviral neuropathy","volume":"267","author":"Sanna","year":"2015","journal-title":"Exp. Neurol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e70080","DOI":"10.1111\/acel.70080","article-title":"Reducing HuD Levels Alleviates Alzheimer\u2019s Disease Pathology in 5xFAD Mice","volume":"24","author":"Ji","year":"2025","journal-title":"Aging Cell"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"9618","DOI":"10.1038\/s41467-024-54004-8","article-title":"HuD impairs neuromuscular junctions and induces apoptosis in human iPSC and Drosophila ALS models","volume":"15","author":"Silvestri","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e10421","DOI":"10.7554\/eLife.10421","article-title":"Regulatory consequences of neuronal ELAV-like protein binding to coding and non-coding RNAs in human brain","volume":"5","author":"Scheckel","year":"2016","journal-title":"eLife"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/15476286.2026.2647903","article-title":"Change of guards: ELAVL proteins switch miRNA export responsibility to regulate differentiation of PC12 cells","volume":"23","author":"Ray","year":"2026","journal-title":"RNA Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"105750","DOI":"10.1016\/j.jbc.2024.105750","article-title":"HuR-miRNA complex Activates RAS GTPase RalA to Facilitate Endosome Targeting and Extracellular Export of miRNAs","volume":"300","author":"Ghosh","year":"2024","journal-title":"J. Biol. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1002\/wrna.4","article-title":"Posttranscriptional regulation of cancer traits by HuR","volume":"1","author":"Abdelmohsen","year":"2010","journal-title":"Wiley Interdiscip. Rev. RNA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1016\/j.str.2025.02.003","article-title":"HuR prevents amyloid beta-induced phase separation of miRNA-bound Ago2 to RNA-processing bodies","volume":"33","author":"Ray","year":"2025","journal-title":"Structure"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Wei, L., and Lai, E.C. (2022). Regulation of the Alternative Neural Transcriptome by ELAV\/Hu RNA Binding Proteins. Front. Genet., 13.","DOI":"10.3389\/fgene.2022.848626"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1634","DOI":"10.1016\/S0960-9822(02)70787-2","article-title":"ELAV, a Drosophila neuron-specific protein, mediates the generation of an alternatively spliced neural protein isoform","volume":"6","author":"Koushika","year":"1996","journal-title":"Curr. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2330","DOI":"10.1016\/j.celrep.2014.11.030","article-title":"ELAVL1 modulates transcriptome-wide miRNA binding in murine macrophages","volume":"9","author":"Lu","year":"2014","journal-title":"Cell Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1016\/j.cell.2006.04.031","article-title":"Relief of microRNA-mediated translational repression in human cells subjected to stress","volume":"125","author":"Bhattacharyya","year":"2006","journal-title":"Cell"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.15252\/embr.201541930","article-title":"Reversible HuR-microRNA binding controls extracellular export of miR-122 and augments stress response","volume":"17","author":"Mukherjee","year":"2016","journal-title":"EMBO Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"111255","DOI":"10.1016\/j.jbc.2026.111255","article-title":"HuR-driven reversible mitochondrial shuttling buffers cytosolic miRNA levels in hepatic cells","volume":"302","author":"Banerjee","year":"2026","journal-title":"J. Biol. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"120200","DOI":"10.1016\/j.bbamcr.2026.120200","article-title":"Sensing the needs: Molecular basis of miRNA regulatory role of ELAVL protein HuR","volume":"1873","author":"Mukherjee","year":"2026","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"113299","DOI":"10.1016\/j.jbc.2026.113299","article-title":"Mechanisms of microRNA Export in Mammalian Cells: From Random Release to Selective Secretion","volume":"302","author":"Bhattacharyya","year":"2026","journal-title":"J. Biol. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"11164","DOI":"10.1523\/JNEUROSCI.2247-12.2012","article-title":"Characterization of multiple exon 1 variants in mammalian HuD mRNA and neuron-specific transcriptional control via neurogenin 2","volume":"32","author":"Bronicki","year":"2012","journal-title":"J. Neurosci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"E4995","DOI":"10.1073\/pnas.1513780112","article-title":"Positive feedback between RNA-binding protein HuD and transcription factor SATB1 promotes neurogenesis","volume":"112","author":"Wang","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1670","DOI":"10.1038\/sj.emboj.7601626","article-title":"Notch3 and the Notch3-upregulated RNA-binding protein HuD regulate Ikaros alternative splicing","volume":"26","author":"Bellavia","year":"2007","journal-title":"EMBO J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1046\/j.1471-4159.2003.01877.x","article-title":"Neuronal HuD gene encoding a mRNA stability regulator is transcriptionally repressed by thyroid hormone","volume":"86","author":"Cuadrado","year":"2003","journal-title":"J. Neurochem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1002\/jnr.23496","article-title":"Alternative role of HuD splicing variants in neuronal differentiation","volume":"93","author":"Hayashi","year":"2015","journal-title":"J. Neurosci. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"101803","DOI":"10.1016\/j.pneurobio.2020.101803","article-title":"miR-129-5p: A key factor and therapeutic target in amyotrophic lateral sclerosis","volume":"190","author":"Loffreda","year":"2020","journal-title":"Prog. Neurobiol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Nasiri-Aghdam, M., Garcia-Gardu\u00f1o, T.C., and Jave-Su\u00e1rez, L.F. (2021). CELF Family Proteins in Cancer: Highlights on the RNA-Binding Protein\/Noncoding RNA Regulatory Axis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222011056"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2273","DOI":"10.1128\/MCB.26.6.2273-2285.2006","article-title":"CARM1 regulates proliferation of PC12 cells by methylating HuD","volume":"26","author":"Fujiwara","year":"2006","journal-title":"Mol. Cell. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Vanevski, F., and Xu, B. (2015). HuD interacts with Bdnf mRNA and is essential for activity-induced BDNF synthesis in dendrites. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0117264"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"12065","DOI":"10.1073\/pnas.0504702102","article-title":"Neuronal ELAV proteins enhance mRNA stability by a PKCalpha-dependent pathway","volume":"102","author":"Pascale","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_37","first-page":"554","article-title":"Role of HuD in nervous system function and pathology","volume":"5","author":"Bird","year":"2013","journal-title":"Front. Biosci. (Schol. Ed.)"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3191","DOI":"10.1091\/mbc.11.9.3191","article-title":"The RNA-binding protein HuD is required for GAP-43 mRNA stability, GAP-43 gene expression, and PKC-dependent neurite outgrowth in PC12 cells","volume":"11","author":"Mobarak","year":"2000","journal-title":"Mol. Biol. Cell"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2142","DOI":"10.1007\/s11064-007-9388-8","article-title":"Coordinated expression of HuD and GAP-43 in hippocampal dentate granule cells during developmental and adult plasticity","volume":"32","author":"Bolognani","year":"2007","journal-title":"Neurochem. Res."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Allen, M., Bird, C., Feng, W., Liu, G., Li, W., Perrone-Bizzozero, N.I., and Feng, Y. (2013). HuD promotes BDNF expression in brain neurons via selective stabilization of the BDNF long 3\u2032UTR mRNA. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0055718"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2303","DOI":"10.1002\/hipo.22048","article-title":"Protein kinase C stimulates HuD-mediated mRNA stability and protein expression of neurotrophic factors and enhances dendritic maturation of hippocampal neurons in culture","volume":"22","author":"Lim","year":"2012","journal-title":"Hippocampus"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"7531","DOI":"10.1074\/jbc.M706082200","article-title":"Post-transcriptional regulation of neuro-oncological ventral antigen 1 by the neuronal RNA-binding proteins ELAV","volume":"283","author":"Ratti","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3650","DOI":"10.1242\/jcs.201244","article-title":"Axonal localization of neuritin\/CPG15 mRNA is limited by competition for HuD binding","volume":"130","author":"Gomes","year":"2017","journal-title":"J. Cell Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2202","DOI":"10.1093\/nar\/30.10.2202","article-title":"HuD binds to three AU-rich sequences in the 3\u2032-UTR of neuroserpin mRNA and promotes the accumulation of neuroserpin mRNA and protein","volume":"30","author":"Cuadrado","year":"2002","journal-title":"Nucleic Acids Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1523\/JNEUROSCI.4626-06.2007","article-title":"The RNA-binding protein HuD binds acetylcholinesterase mRNA in neurons and regulates its expression after axotomy","volume":"27","author":"Mousavi","year":"2007","journal-title":"J. Neurosci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1016\/j.celrep.2014.04.050","article-title":"HuD regulates coding and noncoding RNA to induce APP\u2192A\u03b2 processing","volume":"7","author":"Kang","year":"2014","journal-title":"Cell Rep."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Lim, C.S., and Alkon, D.L. (2014). PKC\u03b5 promotes HuD-mediated neprilysin mRNA stability and enhances neprilysin-induced A\u03b2 degradation in brain neurons. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0097756"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"bpx009","DOI":"10.1093\/biomethods\/bpx009","article-title":"A UV cross-linking method combined with infrared imaging to analyse RNA-protein interactions","volume":"2","author":"Malmqvist","year":"2017","journal-title":"Biol. Methods Protoc."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1967","DOI":"10.1074\/jbc.M106966200","article-title":"HuD, a neuronal-specific RNA-binding protein, increases the in vivo stability of MYCN RNA","volume":"277","author":"Manohar","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"545","DOI":"10.3892\/or.2017.5664","article-title":"Reciprocal antagonistic regulation of N-myc mRNA by miR-17 and the neuronal-specific RNA-binding protein HuD","volume":"38","author":"Samaraweera","year":"2017","journal-title":"Oncol. Rep."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"20511","DOI":"10.1074\/jbc.273.32.20511","article-title":"p21(waf1) mRNA contains a conserved element in its 3\u2019-untranslated region that is bound by the Elav-like mRNA-stabilizing proteins","volume":"273","author":"Joseph","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"16357","DOI":"10.1074\/jbc.M114.599399","article-title":"Mammalian Target of Rapamycin (mTOR) Tagging Promotes Dendritic Branch Variability through the Capture of Ca2+\/Calmodulin-dependent Protein Kinase II \u03b1 (CaMKII\u03b1) mRNAs by the RNA-binding Protein HuD","volume":"290","author":"Sosanya","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1442","DOI":"10.1242\/jcs.02852","article-title":"A role for the ELAV RNA-binding proteins in neural stem cells: Stabilization of Msi1 mRNA","volume":"119","author":"Ratti","year":"2006","journal-title":"J. Cell Sci."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Dell\u2019Orco, M., Oliver, R.J., and Perrone-Bizzozero, N. (2020). HuD Binds to and Regulates Circular RNAs Derived from Neuronal Development- and Synaptic Plasticity-Associated Genes. Front. Genet., 11.","DOI":"10.3389\/fgene.2020.00790"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.molcel.2018.06.032","article-title":"HuD Is a Neural Translation Enhancer Acting on mTORC1-Responsive Genes and Counteracted by the Y3 Small Non-coding RNA","volume":"71","author":"Tebaldi","year":"2018","journal-title":"Mol. Cell"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1083\/jcb.201212089","article-title":"Degradation of high affinity HuD targets releases Kv1.1 mRNA from miR-129 repression by mTORC1","volume":"202","author":"Sosanya","year":"2013","journal-title":"J. Cell Biol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"5105","DOI":"10.1091\/mbc.e06-02-0099","article-title":"A nuclear function of Hu proteins as neuron-specific alternative RNA processing regulators","volume":"17","author":"Zhu","year":"2006","journal-title":"Mol. Biol. Cell"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"4547","DOI":"10.1016\/j.cell.2021.07.003","article-title":"ELAVL4, splicing, and glutamatergic dysfunction precede neuron loss in MAPT mutation cerebral organoids","volume":"184","author":"Bowles","year":"2021","journal-title":"Cell"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"27996","DOI":"10.1074\/jbc.M201982200","article-title":"Poly(A) tail length-dependent stabilization of GAP-43 mRNA by the RNA-binding protein HuD","volume":"277","author":"Miera","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/978-1-61779-034-8_4","article-title":"Posttranscriptional regulation of gene expression in epithelial cells by polyamines","volume":"720","author":"Xiao","year":"2011","journal-title":"Methods Mol. Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1016\/j.molcel.2009.11.013","article-title":"The ELAV protein HuD stimulates cap-dependent translation in a Poly(A)- and eIF4A-dependent manner","volume":"36","author":"Fukao","year":"2009","journal-title":"Mol. Cell"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"3087","DOI":"10.1101\/gad.248902","article-title":"ELAV\/Hu proteins inhibit p27 translation via an IRES element in the p27 5\u2032UTR","volume":"16","author":"Kullmann","year":"2002","journal-title":"Genes Dev."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.gde.2012.12.006","article-title":"Mechanisms coordinating ELAV\/Hu mRNA regulons","volume":"23","author":"Simone","year":"2013","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"157","DOI":"10.4161\/rna.5.3.6782","article-title":"Activity-dependent expression of RNA binding protein HuD and its association with mRNAs in neurons","volume":"5","author":"Tiruchinapalli","year":"2008","journal-title":"RNA Biol."},{"key":"ref_65","first-page":"e90527","article-title":"Advancing Care in Alzheimer\u2019s Disease: Current Treatments and Their Impact on Quality of Life","volume":"17","author":"Yashaeva","year":"2025","journal-title":"Cureus"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"409","DOI":"10.3233\/JAD-2009-0967","article-title":"NELAV proteins alteration in Alzheimer\u2019s disease brain: A novel putative target for amyloid-\u03b2 reverberating on A\u03b2PP processing","volume":"16","author":"Amadio","year":"2009","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1007\/s00439-008-0526-4","article-title":"Replication of association between ELAVL4 and Parkinson disease: The GenePD study","volume":"124","author":"DeStefano","year":"2008","journal-title":"Hum. Genet."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"105211","DOI":"10.1016\/j.nbd.2020.105211","article-title":"HuD regulates SOD1 expression during oxidative stress in differentiated neuroblastoma cells and sporadic ALS motor cortex","volume":"148","author":"Sardone","year":"2021","journal-title":"Neurobiol. Dis."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"jcs258360","DOI":"10.1242\/jcs.258360","article-title":"Amyloid-\u03b2 oligomers block lysosomal targeting of miRNPs to prevent miRNP recycling and target repression in glial cells","volume":"134","author":"De","year":"2021","journal-title":"J. Cell Sci."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1016\/j.omtn.2021.04.008","article-title":"Rheb-mTOR activation rescues A\u03b2-induced cognitive impairment and memory function by restoring miR-146 activity in glial cells","volume":"24","author":"De","year":"2021","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1038\/s41398-024-03075-8","article-title":"MicroRNAs: Pioneering regulators in Alzheimer\u2019s disease pathogenesis, diagnosis, and therapy","volume":"14","author":"Li","year":"2024","journal-title":"Transl. Psychiatry"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"30953","DOI":"10.1038\/srep30953","article-title":"MicroRNA-132\/212 deficiency enhances A\u03b2 production and senile plaque deposition in Alzheimer\u2019s disease triple transgenic mice","volume":"6","author":"Rainone","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"18344","DOI":"10.1074\/jbc.M110.112664","article-title":"MicroRNA-101 regulates amyloid precursor protein expression in hippocampal neurons","volume":"285","author":"Vilardo","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"6415","DOI":"10.1073\/pnas.0710263105","article-title":"Loss of microRNA cluster miR-29a\/b-1 in sporadic Alzheimer\u2019s disease correlates with increased BACE1\/\u03b2-secretase expression","volume":"105","author":"Papadopoulou","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Amakiri, N., Kubosumi, A., Tran, J., and Reddy, P.H. (2019). Amyloid Beta and MicroRNAs in Alzheimer\u2019s Disease. Front. Neurosci., 13.","DOI":"10.3389\/fnins.2019.00430"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1016\/j.omtn.2020.01.010","article-title":"MiRNA-31 Improves Cognition and Abolishes Amyloid-\u03b2 Pathology by Targeting APP and BACE1 in an Animal Model of Alzheimer\u2019s Disease","volume":"19","author":"Carmona","year":"2020","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2426","DOI":"10.1007\/s12035-023-03224-y","article-title":"MicroRNA-650 Regulates the Pathogenesis of Alzheimer\u2019s Disease Through Targeting Cyclin-Dependent Kinase 5","volume":"60","author":"Lin","year":"2023","journal-title":"Mol. Neurobiol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"115613","DOI":"10.1016\/j.expneurol.2025.115613","article-title":"ELAVL1 interacts with APP and promotes A\u03b2-induced apoptosis in Alzheimer\u2019s disease by activating Bcl-2\/Bax signaling","volume":"398","author":"Fu","year":"2026","journal-title":"Exp. Neurol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1007\/s13311-020-00958-8","article-title":"Targeting the RNA-Binding Protein HuR Alleviates Neuroinflammation in Experimental Autoimmune Encephalomyelitis: Potential Therapy for Multiple Sclerosis","volume":"18","author":"Borgonetti","year":"2021","journal-title":"Neurotherapeutics"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2","DOI":"10.61747\/0ifp.202604002","article-title":"Rescue of miRNA export from amyloid-exposed astroglia by Ras homolog enriched in brain (Rheb) protein","volume":"4","author":"Ghosh","year":"2026","journal-title":"Organelle"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"535","DOI":"10.3233\/JAD-160299","article-title":"PKC Activation Counteracts ADAM10 Deficit in HuD-Silenced Neuroblastoma Cells","volume":"54","author":"Marchesi","year":"2016","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"102316","DOI":"10.1016\/j.pneurobio.2022.102316","article-title":"RNA-binding protein ELAVL4\/HuD ameliorates Alzheimer\u2019s disease-related molecular changes in human iPSC-derived neurons","volume":"217","author":"Gerritsen","year":"2022","journal-title":"Prog. Neurobiol."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Xu, D., Di, K., Fan, B., Wu, J., Gu, X., Sun, Y., Khan, A., Li, P., and Li, Z. (2022). MicroRNAs in extracellular vesicles: Sorting mechanisms, diagnostic value, isolation, and detection technology. Front. Bioeng. Biotechnol., 10.","DOI":"10.3389\/fbioe.2022.948959"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1016\/j.ymthe.2021.11.006","article-title":"Microglia secrete miR-146a-5p-containing exosomes to regulate neurogenesis in depression","volume":"30","author":"Fan","year":"2022","journal-title":"Mol. Ther."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"107170","DOI":"10.1016\/j.jbc.2024.107170","article-title":"Human antigen R transfers miRNA to Syntaxin 5 to synergize miRNA export from activated macrophages","volume":"300","author":"Choudhury","year":"2024","journal-title":"J. Biol. Chem."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"7105","DOI":"10.1074\/jbc.M112.410944","article-title":"Neuronal Exosomal miRNA-dependent Translational Regulation of Astroglial Glutamate Transporter GLT1","volume":"288","author":"Morel","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"e2015454118","DOI":"10.1073\/pnas.2015454118","article-title":"MiR-124 synergism with ELAVL3 enhances target gene expression to promote neuronal maturity","volume":"118","author":"Lu","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1038\/onc.2015.235","article-title":"RNA-binding protein HuR sequesters microRNA-21 to prevent translation repression of proinflammatory tumor suppressor gene programmed cell death 4","volume":"35","author":"Poria","year":"2016","journal-title":"Oncogene"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s10020-021-00271-w","article-title":"ELAVL1 is transcriptionally activated by FOXC1 and promotes ferroptosis in myocardial ischemia\/reperfusion injury by regulating autophagy","volume":"27","author":"Chen","year":"2021","journal-title":"Mol. Med."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/s41419-022-04792-y","article-title":"Loss of RNA binding protein HuD facilitates the production of the senescence-associated secretory phenotype","volume":"13","author":"Ryu","year":"2022","journal-title":"Cell Death Dis."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1007\/s00401-021-02374-4","article-title":"Nuclear depletion of RNA-binding protein ELAVL3 (HuC) in sporadic and familial amyotrophic lateral sclerosis","volume":"142","author":"Ko","year":"2021","journal-title":"Acta Neuropathol."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Viiri, J., Amadio, M., Marchesi, N., Hyttinen, J.M., Kivinen, N., Sironen, R., Rilla, K., Akhtar, S., Provenzani, A., and D\u2019Agostino, V.G. (2013). Autophagy activation clears ELAVL1\/HuR-mediated accumulation of SQSTM1\/p62 during proteasomal inhibition in human retinal pigment epithelial cells. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0069563"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Guo, D., Yan, J., Yang, Z., Chen, M., Zhong, W., Yuan, X., and Yu, S. (2024). The immune regulatory role of exosomal miRNAs and their clinical application potential in heart failure. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1476865"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1212\/CPJ.0000000000000117","article-title":"HIV-associated neurocognitive disorders: Five new things","volume":"5","author":"Rumbaugh","year":"2015","journal-title":"Neurol. Clin. Pract."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1111\/jnc.14640","article-title":"HIV gp120-induced neuroinflammation potentiates NMDA receptors to overcome basal suppression of inhibitory synapses by p38 MAPK","volume":"148","author":"Zhang","year":"2019","journal-title":"J. Neurochem."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Pacwa, A., Machowicz, J., Akhtar, S., Rodak, P., Liu, X., Pietrucha-Dutczak, M., Lewin-Kowalik, J., Amadio, M., and Smedowski, A. (2023). Deficiency of the RNA-binding protein ELAVL1\/HuR leads to the failure of endogenous and exogenous neuroprotection of retinal ganglion cells. Front. Cell. Neurosci., 17.","DOI":"10.3389\/fncel.2023.1131356"},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Thompson, L.J., Genovese, J., Hong, Z., Singh, M.V., and Singh, V.B. (2024). HIV-Associated Neurocognitive Disorder: A Look into Cellular and Molecular Pathology. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25094697"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1002\/wrna.1162","article-title":"Regulation of stress granules and P-bodies during RNA virus infection","volume":"4","author":"Lloyd","year":"2013","journal-title":"Wiley Interdiscip. Rev. RNA"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.chom.2008.03.004","article-title":"P bodies, stress granules, and viral life cycles","volume":"3","author":"Beckham","year":"2008","journal-title":"Cell Host Microbe"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.virol.2009.06.050","article-title":"The Elav-like protein HuR exerts translational control of viral internal ribosome entry sites","volume":"392","author":"Ramdohr","year":"2009","journal-title":"Virology"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"16965","DOI":"10.1038\/s41598-017-16793-5","article-title":"Elucidating the in vivo interactome of HIV-1 RNA by hybridization capture and mass spectrometry","volume":"7","author":"Knoener","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.1021\/pr9006987","article-title":"Identification of Novel Interacting Protein Partners of SMN Using Tandem Affinity Purification","volume":"9","author":"Shafey","year":"2010","journal-title":"J. Proteome Res."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Marchesi, N., Linciano, P., Campagnoli, L.I.M., Fahmideh, F., Rossi, D., Costa, G., Ambrosio, F.A., Barbieri, A., Collina, S., and Pascale, A. (2023). Short- and Long-Term Regulation of HuD: A Molecular Switch Mediated by Folic Acid?. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241512201"},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Caillet-Boudin, M.L., Fernandez-Gomez, F.J., Tran, H., Dhaenens, C.M., Buee, L., and Sergeant, N. (2014). Brain pathology in myotonic dystrophy: When tauopathy meets spliceopathy and RNAopathy. Front. Mol. Neurosci., 6.","DOI":"10.3389\/fnmol.2013.00057"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1074\/jbc.M113.474700","article-title":"The RNA-binding protein HuD regulates autophagosome formation in pancreatic \u03b2 cells by promoting autophagy-related gene 5 expression","volume":"289","author":"Kim","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"3914","DOI":"10.1523\/JNEUROSCI.3631-10.2011","article-title":"The survival of motor neuron (SMN) protein interacts with the mRNA-binding protein HuD and regulates localization of poly(A) mRNA in primary motor neuron axons","volume":"31","author":"Fallini","year":"2011","journal-title":"J. Neurosci."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/18\/1649\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T17:19:30Z","timestamp":1789147170000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/18\/1649"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,11]]},"references-count":106,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["cells15181649"],"URL":"https:\/\/doi.org\/10.3390\/cells15181649","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,11]]}}}