Neurodegenerative disease-associated microRNAs acting as signaling molecules modulate CNS neuron structure and viability
Open accessAbstract
Background: Dysregulation of microRNA (miRNA) expression in the brain is a common feature of neurodegenerative diseases. Beyond their conventional role in regulating gene expression at the post-transcriptional level, certain miRNAs can act extracellularly as signaling molecules. Our study elucidates the identity of such miRNA species serving as ligands for membrane receptors expressed in central nervous system (CNS) neurons and the impact of such miRNAs on neurons in the context of neurodegenerative disease. Methods: We combined a machine learning approach with the analysis of disease-associated miRNA databases to predict Alzheimer’s disease (AD)-associated miRNAs as potential signaling molecules for single-stranded RNA-sensing Toll-like receptors (TLRs) 7 and 8. TLR-expressing HEK-Blue reporter cells, primary murine microglia, and human THP-1 macrophages were used to validate the AD miRNAs as ligands for human and mouse TLR7 and/or TLR8. Interaction between mouse cortical neurons and extracellularly applied AD miRNAs was analyzed by live cell imaging and confocal microscopy. Transcriptome changes in cortical neurons exposed to AD miRNAs were assessed by RNAseq and RT-qPCR. The extracellular AD miRNAs’ effects on CNS neuron structure were investigated in cell cultures of murine primary cortical neurons and iPSC-derived human cortical neurons by immunocytochemistry. We employed a mouse model of intrathecal injection to assess effects of AD miRNAs acting as signaling molecules on neurons in vivo. Results: We identified the AD-associated miRNAs miR-124-5p, miR-92a-1-5p, miR-9-5p, and miR-501-3p as novel endogenous ligands for TLR7 and/or TLR8. These miRNAs being extracellularly stable and active were taken up by murine cortical neurons via endocytosis and induced changes in neuronal inflammation-, proliferation-, and apoptosis-related gene expression. Exposure of both murine and human cortical neurons to the AD-associated miRNAs led to alterations of dendrite and axon structure, synapse protein expression, and cell viability in a sequence-dependent fashion. Extracellular introduction of the AD miRNAs into the cerebrospinal fluid of mice resulted in both changes in neuronal structure and synapses, and neuronal loss in the cerebral cortex. Most of the observed extracellular miRNA-induced effects on cortical neurons involved TLR7/8 signaling. Conclusion: Neurodegenerative disease-associated miRNAs in extracellular form act as signaling molecules for CNS neurons including human cortical neurons, thereby modulating their structure and viability.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cited works that were retracted
Works this paper cites that were later retracted, from the retraction notices publishers deposit. Major when the notice came out before this paper was published.
Cites a retracted work: 10.18632/oncotarget.23119
InfoThe cited work was retracted on 2025-12-31 (notice 10.18632/oncotarget.28815), not before this paper was published (2025-04-24).
Cited work 10.18632/oncotarget.23119 · retracted 2025-12-31 · notice 10.18632/oncotarget.28815 · this paper published 2025-04-24
“An F, Gong G, Wang Y, Bian M, Yu L, Wei C. MiR-124 acts as a target for Alzheimer’s disease by regulating BACE1. Oncotarget. 2017;8(69):114065.”
Cites
1 retracted
MiR-124 acts as a target for Alzheimer’s disease by regulating BACE1
An, F.-M., Gong, G.-H., Wang, Y., Bian, M., Li-jun, Y., & Wei, C. (2017) · Oncotarget · doi:10.18632/oncotarget.23119 · Cited by 129 · see citing works
RetractedModerated estimation of fold change and dispersion for RNA-seq data with DESeq2
Love, M. I., Huber, W., & Anders, S. (2014) · Genome Biology · doi:10.1186/s13059-014-0550-8 · Cited by 95,106 · see citing works
STAR: ultrafast universal RNA-seq aligner
Dobin, A., Davis, C. A., Schlesinger, F., Drenkow, J., Zaleski, C., Jha, S., Batut, P., Chaisson, M., & Gingeras, T. R. (2013) · Bioinformatics · doi:10.1093/bioinformatics/bts635 · Cited by 51,709 · see citing works
featureCounts: an efficient general purpose program for assigning sequence reads to genomic features
Liao, Y., Smyth, G. K., & Shi, W. (2014) · Bioinformatics · doi:10.1093/bioinformatics/btt656 · Cited by 27,219 · see citing works
The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors
Kawai, T., & Akira, S. (2010) · Nature Immunology · doi:10.1038/ni.1863 · Cited by 9,304 · see citing works
Circulating microRNAs as stable blood-based markers for cancer detection
Mitchell, P. S., Parkin, R. K., Kroh, E. M., Fritz, B. R., Wyman, S. K., Pogosova-Agadjanyan, E. L., Peterson, A., Noteboom, J., O'Briant, K. C., Allen, A., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0804549105 · Cited by 7,969 · see citing works
Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8
Heil, F., Hemmi, H., Hochrein, H., Ampenberger, F., Kirschning, C., Akira, S., Lipford, G., Wagner, H., & Bauer, S. (2004) · Science · doi:10.1126/science.1093620 · Cited by 3,947 · see citing works
Mammalian microRNAs predominantly act to decrease target mRNA levels
Guo, H., Ingolia, N. T., Weissman, J. S., & Bartel, D. P. (2010) · Nature · doi:10.1038/nature09267 · Cited by 3,886 · see citing works
Toll-like receptors and their crosstalk with other innate receptors in infection and immunity
Kawai, T., & Akira, S. (2011) · Immunity · doi:10.1016/j.immuni.2011.05.006 · Cited by 3,658 · see citing works
Knopman, D. S., Amieva, H., Petersen, R. C., Chételat, G., Holtzman, D. M., Hyman, B. T., Nixon, R. A., & Jones, D. T. (2021) · Nature Reviews Disease Primers · doi:10.1038/s41572-021-00269-y · Cited by 2,606 · see citing works
Small anti-viral compounds activate immune cells via the TLR7 MyD88–dependent signaling pathway
Hemmi, H., Kaisho, T., Takeuchi, O., Sato, S., Sanjo, H., Hoshino, K., Horiuchi, T., Tomizawa, H., Takeda, K., & Akira, S. (2002) · Nature Immunology · doi:10.1038/ni758 · Cited by 2,517 · see citing works
Dynasore, a Cell-Permeable Inhibitor of Dynamin
Macia, E., Ehrlich, M., Massol, R., Boucrot, E., Brunner, C., & Kirchhausen, T. L. (2006) · Developmental Cell · doi:10.1016/j.devcel.2006.04.002 · Cited by 2,038 · see citing works
Towards a molecular understanding of microRNA-mediated gene silencing
Jonas, S., & Izaurralde, E. (2015) · Nature Reviews Genetics · doi:10.1038/nrg3965 · Cited by 1,872 · see citing works
Hallmarks of neurodegenerative diseases
Wilson, D. M., Cookson, M. R., Van Den Bosch, L., Zetterberg, H., Holtzman, D. M., & Dewachter, I. (2023) · Cell · doi:10.1016/j.cell.2022.12.032 · Cited by 1,789 · see citing works
Rapid single-step induction of functional neurons from human pluripotent stem cells
Zhang, Y., Pak, C., Han, Y., Ahlenius, H., Zhang, Z., Chanda, S., Marro, S., Patzke, C., Acuna, C., Covy, J., et al. (2013) · Neuron · doi:10.1016/j.neuron.2013.05.029 · Cited by 1,644 · see citing works
MicroRNAs bind to Toll-like receptors to induce prometastatic inflammatory response
Fabbri, M., Paone, A., Calore, F., Galli, R., Gaudio, E., Santhanam, R., Lovat, F., Fadda, P., Mao, C., Nuovo, G. J., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1209414109 · Cited by 1,558 · see citing works
Noncoding RNA therapeutics—Challenges and potential solutions
Winkle, M., El-Daly, S. M., Fabbri, M., & Calin, G. A. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00219-z · Cited by 1,551 · see citing works
siRNA versus miRNA as therapeutics for gene silencing
Lam, J. K. W., Chow, M. Y. T., Zhang, Y., & Leung, S. W. S. (2015) · Molecular Therapy — Nucleic Acids · doi:10.1038/mtna.2015.23 · Cited by 1,081 · see citing works
Lehnardt, S., Massillon, L., Follett, P., Jensen, F. E., Ratan, R., Rosenberg, P. A., Volpe, J. J., & Vartanian, T. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1432609100 · Cited by 1,052 · see citing works
Self-citationHuman TLR7 or TLR8 independently confer responsiveness to the antiviral compound R-848
Jurk, M., Heil, F., Vollmer, J., Schetter, C., Krieg, A. Μ., Wagner, H., Lipford, G. B., & Bauer, S. (2002) · Nature Immunology · doi:10.1038/ni0602-499 · Cited by 1,017 · see citing works
Cogswell, J. P., Ward, J., Taylor, I. A., Waters, M., Shi, Y., Cannon, B., Kelnar, K., Kemppainen, J., Brown, D., Chen, C., et al. (2008) · Journal of Alzheimer s Disease · doi:10.3233/jad-2008-14103 · Cited by 943 · see citing works
Spandidos, A., Wang, X., Wang, H., & Seed, B. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkp1005 · Cited by 900 · see citing works
Kim, C., Ho, D.-H., Suk, J.-E., You, S., Michael, S., Kang, J., Joong Lee, S., Masliah, E., Hwang, D., Lee, H.-J., et al. (2013) · Nature Communications · doi:10.1038/ncomms2534 · Cited by 856 · see citing works
Secreted microRNAs: a new form of intercellular communication
Chen, X., Liang, H., Zhang, J., Zen, K., & Zhang, C. (2012) · Trends in Cell Biology · doi:10.1016/j.tcb.2011.12.001 · Cited by 761 · see citing works
An unconventional role for miRNA: let-7 activates toll-like receptor 7 and causes neurodegeneration
Lehmann, S. M., Krüger, C., Park, B., Derkow, K., Rosenberger, K., Baumgart, J., Trimbuch, T., Eom, G., Hinz, M., Kaul, D., et al. (2012) · Nature Neuroscience · doi:10.1038/nn.3113 · Cited by 697 · see citing works
Self-citationMicro-RNA speciation in fetal, adult and Alzheimer's disease hippocampus
Lukiw, W. J. (2007) · Neuroreport · doi:10.1097/wnr.0b013e3280148e8b · Cited by 662 · see citing works
Cellular uptake and trafficking of antisense oligonucleotides
Crooke, S. T., Wang, S., Vickers, T. A., Shen, W., & Liang, X.-H. (2017) · Nature Biotechnology · doi:10.1038/nbt.3779 · Cited by 582 · see citing works
Eichhorn, S. W., Guo, H., McGeary, S. E., Rodríguez‐Mias, R. A., Shin, C., Baek, D., Hsu, S., Ghoshal, K., Villén, J., & Bartel, D. P. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.08.028 · Cited by 491 · see citing works
TLR2 Is a Primary Receptor for Alzheimer’s Amyloid β Peptide To Trigger Neuroinflammatory Activation
Liu, S., Liu, Y., Hao, W., Wolf, L., Kiliaan, A. J., Penke, B., Rübe, C. E., Walter, J., Heneka, M. T., Hartmann, T., et al. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1101121 · Cited by 439 · see citing works
microRNA dysregulation in neurodegenerative diseases: A systematic review
Juźwik, C. A., Drake, S., Zhang, Y., Paradis-Isler, N., Sylvester, A., Amar‐Zifkin, A., Douglas, C., Morquette, B., Moore, C. S., & Fournier, A. E. (2019) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2019.101664 · Cited by 436 · see citing works
Stein, C. A., Hansen, J. B., Lai, J. C. H., Wu, S., Voskresenskiy, A. M., H⊘g, A., Worm, J., Hedtjärn, M., Souleimanian, N. E., Miller, P. S., et al. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkp841 · Cited by 384 · see citing works
Men, Y., Yelick, J., Jin, S., Tian, Y., Chiang, M. S. R., Higashimori, H., Brown, E., Jarvis, R., & Yang, Y. (2019) · Nature Communications · doi:10.1038/s41467-019-11534-w · Cited by 331 · see citing works
Innate Immunity and Neurodegeneration
Labzin, L. I., Heneka, M. T., & Latz, E. (2018) · Annual Review of Medicine · doi:10.1146/annurev-med-050715-104343 · Cited by 319 · see citing works
Identification of RNA Sequence Motifs Stimulating Sequence-Specific TLR8-Dependent Immune Responses
Forsbach, A., Némorin, J.-G., Montino, C., Müller, C., Samulowitz, U., Vicari, A. P., Jurk, M., Mutwiri, G., Krieg, A. Μ., Lipford, G. B., et al. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.6.3729 · Cited by 316 · see citing works
Extracellular MicroRNAs Activate Nociceptor Neurons to Elicit Pain via TLR7 and TRPA1
Park, C., Xu, Z., Berta, T., Han, Q., Chen, G., Liu, X., & Ji, R. (2014) · Neuron · doi:10.1016/j.neuron.2014.02.011 · Cited by 316 · see citing works
Veremeyko, T., Kuznetsova, I. S., Dukhinova, M., Yung, A. W. Y., Kopeikina, E., Barteneva, N. S., & Ponomarev, E. D. (2018) · Journal of Neuroscience Research · doi:10.1002/jnr.24344 · Cited by 304 · see citing works
Koller, E., Vincent, T. M., Chappell, A. E., De, S., Manoharan, M., & Bennett, C. F. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkr089 · Cited by 284 · see citing works
Ma, Y., Li, J., Chiu, I., Wang, Y., Sloane, J., Lu, J.-N., Kosaras, B., Sidman, R., Volpe, J., & Vartanian, T. (2006) · Journal of Cell Biology · doi:10.1083/jcb.200606016 · Cited by 284 · see citing works
PhenomiR: a knowledgebase for microRNA expression in diseases and biological processes
Ruepp, A., Kowarsch, A., Schmidl, D., Buggenthin, F., Brauner, B., Dunger-Kaltenbach, I., Fobo, G., Frishman, G., Montrone, C., & Theis, F. J. (2010) · Genome biology · doi:10.1186/gb-2010-11-1-r6 · Cited by 283 · see citing works
Cell-Type-Based Analysis of MicroRNA Profiles in the Mouse Brain
He, M., Liu, Y., Wang, X., Zhang, M. Q., Hannon, G. J., & Huang, Z. J. (2012) · Neuron · doi:10.1016/j.neuron.2011.11.010 · Cited by 277 · see citing works
Sasaki, Y., Vohra, B., Lund, F., & Milbrandt, J. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.5469-08.2009 · Cited by 254 · see citing works
Microvesicles containing miRNAs promote muscle cell death in cancer cachexia via TLR7
He, W. A., Calore, F., Londhe, P., Canella, A., D, D. C. G., & Croce, C. M. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1402714111 · Cited by 251 · see citing works
Dynamin triple knockout cells reveal off target effects of commonly used dynamin inhibitors
Park, R. J.-H., Shen, H., Liu, L., Liu, X., Ferguson, S. M., & Camilli, P. V. D. (2013) · Journal of Cell Science · doi:10.1242/jcs.138578 · Cited by 249 · see citing works
(2012) · PubMed Central · Cited by 248 · see citing works
Cellular Uptake and Intracellular Trafficking of Antisense and siRNA Oligonucleotides
Juliano, R. L., Ming, X., & Nakagawa, O. (2011) · Bioconjugate Chemistry · doi:10.1021/bc200377d · Cited by 193 · see citing works
Glial toll-like receptor signaling in central nervous system infection and autoimmunity
Carpentier, P. A., Duncan, D. S., & Miller, S. D. (2007) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2007.08.011 · Cited by 178 · see citing works
Rapid Ngn2-induction of excitatory neurons from hiPSC-derived neural progenitor cells
Ho, S., Hartley, B. J., Julia, T. C. W., Beaumont, M. A., Stafford, K., Slesinger, P. A., & Brennand, K. (2015) · Methods · doi:10.1016/j.ymeth.2015.11.019 · Cited by 173 · see citing works
Differential expression of microRNAs in Alzheimer's disease brain, blood, and cerebrospinal fluid
Takousis, P., Sadlon, A., Schulz, J., Wohlers, I., Dobričić, V., Middleton, L. T., Lill, C. M., Perneczky, R., & Bertram, L. (2019) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2019.06.4952 · Cited by 173 · see citing works
Serum microRNA miR-501-3p as a potential biomarker related to the progression of Alzheimer’s disease
Hara, N., Kikuchi, M., Miyashita, A., Hatsuta, H., Saito, Y., Kasuga, K., Murayama, S., Ikeuchi, T., & Kuwano, R. (2017) · Acta Neuropathologica Communications · doi:10.1186/s40478-017-0414-z · Cited by 163 · see citing works
Endosomal escape of RNA therapeutics: How do we solve this rate-limiting problem?
Dowdy, S. F. (2023) · RNA · doi:10.1261/rna.079507.122 · Cited by 160 · see citing works
Hydrophobically Modified siRNAs Silence Huntingtin mRNA in Primary Neurons and Mouse Brain
Alterman, J. F., Hall, L. M., Coles, A. H., Hassler, M. R., Didiot, M.-C., Chase, K., Abraham, J., Sottosanti, E., Johnson, E., Sapp, E., et al. (2015) · Molecular Therapy - Nucleic Acids · doi:10.1038/mtna.2015.38 · Cited by 158 · see citing works
miRNATissueAtlas2: an update to the human miRNA tissue atlas
Keller, A., Gröger, L., Tschernig, T., Solomon, J., Laham, O., Schaum, N., Wagner, V., Kern, F., Schmartz, G. P., Li, Y., et al. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkab808 · Cited by 143 · see citing works
Riancho, J., Vázquez-Higuera, J. L., Pozueta, A., Lage, C., Kazimierczak, M., Bravo, M., Calero, M., Gonalezález, A., Rodríguez, E., Lleó, A., et al. (2017) · Journal of Alzheimer's Disease · doi:10.3233/jad-161179 · Cited by 143 · see citing works
Saucier, D., Wajnberg, G., Roy, J. W., Beauregard, A., Chacko, S. M., Crapoulet, N., Fournier, S., Ghosh, A., Lewis, S. M., Marrero, A., et al. (2018) · Brain Research · doi:10.1016/j.brainres.2018.12.016 · Cited by 135 · see citing works
Human endogenous retrovirus HERV-K(HML-2) RNA causes neurodegeneration through Toll-like receptors
Dembny, P., Newman, A. G., Singh, M., Hinz, M., Szczepek, M., Krüger, C., Adalbert, R., Dzaye, O., Trimbuch, T., Wallach, T., et al. (2020) · JCI Insight · doi:10.1172/jci.insight.131093 · Cited by 134 · see citing works
Self-citationmicroRNAs as neuroregulators, biomarkers and therapeutic agents in neurodegenerative diseases
Basak, I., Patil, K. S., Alves, G. W., Larsen, J. P., & Møller, S. G. (2015) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-015-2093-x · Cited by 120 · see citing works
Gene set enrichment for reproducible science: comparison of CERNO and eight other algorithms
Żyła, J., Marczyk, M., Domaszewska, T., Kaufmann, S. H. E., Polańska, J., & Weiner, J. M. (2019) · Bioinformatics · doi:10.1093/bioinformatics/btz447 · Cited by 118 · see citing works
Hébert, S. S., Wang, W.-X., Zhu, Q., & Nelson, P. T. (2013) · Journal of Alzheimer's Disease · doi:10.3233/jad-122350 · Cited by 110 · see citing works
TLR8: An Innate Immune Receptor in Brain, Neurons and Axons
Ma, Y., Haynes, R., Sidman, R., & Vartanian, T. (2007) · Cell Cycle · doi:10.4161/cc.6.23.5018 · Cited by 104 · see citing works
Rosenberger, K., Derkow, K., Dembny, P., Krüger, C., Schott, E., & Lehnardt, S. (2014) · Journal of Neuroinflammation · doi:10.1186/s12974-014-0166-7 · Cited by 91 · see citing works
Self-citationHung, Y.-F., Chen, C.-Y., Shih, Y.-C., Liu, H.-Y., Huang, C.-M., & Hsueh, Y.-P. (2018) · Journal of Cell Biology · doi:10.1083/jcb.201712113 · Cited by 86 · see citing works
microRNAs are ligands of Toll-like receptors
Chen, X., Liang, H., Zhang, J., Zen, K., & Zhang, C. (2013) · RNA · doi:10.1261/rna.036319.112 · Cited by 84 · see citing works
TLR7 Negatively Regulates Dendrite Outgrowth through the Myd88-c-Fos-IL-6 Pathway
Liu, H., Hong, Y.-F., Huang, C.-M., Chen, C., Huang, T., & Hsueh, Y. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.5566-12.2013 · Cited by 75 · see citing works
Extracellularly Delivered Single-Stranded Viral RNA Causes Neurodegeneration Dependent on TLR7
Lehmann, S. M., Rosenberger, K., Krüger, C., Habbel, P., Derkow, K., Kaul, D., Rybak‐Wolf, A., Brandt, C., Schott, E., Wulczyn, F. G., et al. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1201078 · Cited by 75 · see citing works
Self-citationFrederiksen, H. R. S., Haukedal, H., & Freude, K. (2019) · BioMed Research International · doi:10.1155/2019/7420189 · Cited by 68 · see citing works
SARM1, Not MyD88, Mediates TLR7/TLR9-Induced Apoptosis in Neurons
Mukherjee, P., Winkler, C. W., Taylor, K., Woods, T. A., Nair, V., Khan, B. A., & Peterson, K. E. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1500953 · Cited by 66 · see citing works
Liu, H., Huang, C.-M., Hung, Y.-F., & Hsueh, Y. (2015) · Experimental Neurology · doi:10.1016/j.expneurol.2015.04.011 · Cited by 64 · see citing works
Xu, J., Chen, Q., Zen, K., Zhang, C., & Zhang, Q. (2013) · Journal of Neurochemistry · doi:10.1111/jnc.12057 · Cited by 61 · see citing works
Stability of circulating microRNAs in serum
Kupec, T., Bleilevens, A., Iborra, S., Najjari, L., Wittenborn, J., Maurer, J., & Stickeler, E. (2022) · PLoS ONE · doi:10.1371/journal.pone.0268958 · Cited by 60 · see citing works
Wallach, T., Mossmann, Z. J., Szczepek, M., Wetzel, M., Machado, R. S. R., Raden, M., Miladi, M., Kleinau, G., Krüger, C., Dembny, P., et al. (2021) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00498-5 · Cited by 48 · see citing works
Self-citationSIDT2 mediates gymnosis, the uptake of naked single-stranded oligonucleotides into living cells
Takahashi, M., Contu, V. R., Kabuta, C., Hase, K., Fujiwara, Y., Wada, K., & Kabuta, T. (2017) · RNA Biology · doi:10.1080/15476286.2017.1302641 · Cited by 45 · see citing works
Domaszewska, T., Scheuermann, L., Hahnke, K., Mollenkopf, H., Dorhoi, A., Kaufmann, S. H. E., & Weiner, J. M. (2017) · Scientific Reports · doi:10.1038/s41598-017-11812-x · Cited by 44 · see citing works
Ran-dependent TPX2 activation promotes acentrosomal microtubule nucleation in neurons
Chen, W., Chen, Y., Huang, Y., Hsieh, B.-Y., Chiu, H.-C., Kao, P.-Y., Chao, C.-Y., & Hwang, E. (2017) · Scientific Reports · doi:10.1038/srep42297 · Cited by 43 · see citing works
MorphoNeuroNet: An automated method for dense neurite network analysis
Pani, G., Vos, W. H. D., Samari, N., de Saint‐Georges, L., Baatout, S., Oostveldt, P. V., & Benotmane, M. A. (2013) · Cytometry Part A · doi:10.1002/cyto.a.22408 · Cited by 42 · see citing works
Pomper, N., Liu, Y., Hoye, M. L., Dougherty, J. D., & Miller, T. M. (2020) · Scientific Reports · doi:10.1038/s41598-020-61307-5 · Cited by 39 · see citing works
Li, H., Wu, C., Aramayo, R., Sachs, M. S., & Harlow, M. L. (2015) · Scientific Reports · doi:10.1038/srep14918 · Cited by 36 · see citing works
Vocelle, D. B., Chan, C., & Walton, S. P. (2019) · Nucleic Acid Therapeutics · doi:10.1089/nat.2019.0804 · Cited by 36 · see citing works
Das, D., Peng, X., Lam, A.-T. N., Bader, J. S., & Avramopoulos, D. (2021) · Schizophrenia Research · doi:10.1016/j.schres.2020.12.041 · Cited by 36 · see citing works
Byrnes, A. E., Domínguez, S. L., Yen, C., Laufer, B. I., Foreman, O., Reichelt, M., Lin, H., Sagolla, M. S., Hötzel, K., Ngu, H., et al. (2023) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2023.05.005 · Cited by 35 · see citing works
Wallach, T. E., Wetzel, M., Dembny, P., Staszewski, O., Krüger, C., Buonfiglioli, A., Prinz, M., & Lehnardt, S. (2020) · Cells · doi:10.3390/cells9010186 · Cited by 27 · see citing works
Self-citationIs endocytosis by caveolae dependent on dynamin?
Parton, R. G., Taraska, J. W., & Lundmark, R. (2024) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-024-00735-x · Cited by 23 · see citing works
High-content analysis of neuronal morphology in human iPSC-derived neurons
Lickfett, S., Menacho, C., Zink, A., Telugu, N. S., Beller, M., Diecke, S., Cambridge, S. B., & Prigione, A. (2022) · STAR Protocols · doi:10.1016/j.xpro.2022.101567 · Cited by 22 · see citing works
MiRNA-501-3p and miRNA-502-3p: a promising biomarker panel for Alzheimer’s disease
Devara, D., Sharma, B., Goyal, G., Rodarte, D., Kulkarni, A., Tinu, N., Pai, A., & Kumar, S. (2025) · Clinical and Translational Medicine · doi:10.1002/ctm2.70389 · Cited by 15 · see citing works
Structure-aware machine learning identifies microRNAs operating as Toll-like receptor 7/8 ligands
Raden, M., Wallach, T., Miladi, M., Zhai, Y., Krüger, C., Mossmann, Z. J., Dembny, P., Backofen, R., & Lehnardt, S. (2021) · RNA Biology · doi:10.1080/15476286.2021.1940697 · Cited by 14 · see citing works
Self-citationMicroRNA-based recent research developments in Alzheimer's disease
Ramirez-Gomez, J., Dalal, S., Devara, D., Sharma, B., Rodarte, D., & Kumar, S. (2025) · Journal of Alzheimer s Disease · doi:10.1177/13872877241313397 · Cited by 14 · see citing works
miR-154-5p Is a Novel Endogenous Ligand for TLR7 Inducing Microglial Activation and Neuronal Injury
McGurran, H., Kumbol, V. W.-A., Krüger, C., Wallach, T., & Lehnardt, S. (2024) · Cells · doi:10.3390/cells13050407 · Cited by 12 · see citing works
Self-citationSagar, R., Azoidis, I., Zivko, C., Xydia, A., Oh, E. S., Rosenberg, P. B., Lyketsos, C. G., Mahairaki, V., & Avramopoulos, D. (2023) · Cells · doi:10.3390/cells12151990 · Cited by 9 · see citing works
The Unconventional Biophysical Function of MicroRNA-1 in Modulating Cardiac Electrophysiology
Yang, D. (2020) · Biophysical Journal · doi:10.1016/j.bpj.2019.11.2707 · Cited by 1 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The Gut–brain–immune Triad in Neurodegeneration: An Integrated Perspective
Chakrabarti, S. K., & Chattopadhyay, D. (2025) · Journal of Translational Gastroenterology · doi:10.14218/jtg.2025.00027 · Cited by 4 · see citing works
MicroRNA-29a-5p contributes to neuroinflammation through TLR7
McGurran, H., Graceffo, E., Kumbol, V. W.-A., Jendrach, M., Hinkelmann, L., Brehm, M., Ravatt, L. M., Krüger, C., Wallach, T., Haake, A., et al. (2026) · Journal of Neuroinflammation · doi:10.1186/s12974-025-03680-4 · Cited by 4 · see citing works
Self-citationZhao, Y., Zhuang, L., Ma, J., Ma, M., & Zhang, Y. (2026) · Talanta · doi:10.1016/j.talanta.2026.129510 · Cited by 4 · see citing works
Extracellular microRNAs modulate human microglial function through TLR8
Weidling, H., Motta, E., Kuhrt, L. D., Krüger, C., Figueiredo, C. A., Wallach, T., Frahm, S., Diecke, S., Wolf, S. A., Kettenmann, H., et al. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1645062 · Cited by 3 · see citing works
Self-citationMitochondria-Associated MicroRNAs: Emerging Roles in the Pathogenesis of Parkinson’s Disease
Catanesi, M., Leandro, L. D., Colasante, M., Cimini, A., d’Angelo, M., Castelli, V., Obreja, C. M., & Ippoliti, R. (2026) · Biomedicines · doi:10.3390/biomedicines14020313 · Cited by 3 · see citing works
Chen, Z., Liu, Y., Wang, H., Liu, K., Li, Y., Hu, X., Li, R., & Sun, L. (2026) · Alzheimer s Research & Therapy · doi:10.1186/s13195-026-02048-x
Extracellular Vesicle-Derived microRNAs as Diagnostic Biomarkers Across Neurodegenerative Diseases
Tevlek, A. (2026) · IntechOpen eBooks · doi:10.5772/intechopen.1017741
Toll-like receptor signaling modulates AMPA receptor trafficking in homeostatic synaptic downscaling
Koga, A., 周平, 貴., & Matsuda, S. (2026) · The Journal of Physiological Sciences · doi:10.1016/j.jphyss.2026.100112
- Authors
- Kumbol, V., Ivanov, A., McGurran, H., Schüler, J., Zhai, Y., Ludwik, K., Hinkelmann, L., Brehm, M., Krüger, C., Küchler, J., Wallach, T., Höltje, M., Beule, D., Stachelscheid, H., & Lehnardt, S.
- Affiliations
- Humboldt-Universität zu Berlin (DE)
- Berlin Institute of Health at Charité - Universitätsmedizin Berlin (DE)
- Corresponding author
- Lehnardt, Seija
- ORCID
- Venue
- Cell Communication and Signaling
- Published
- 2025-04-24
- Volume
- 23
- Issue
- 1
- Pages
- 196-196
- ISSN
- 1478-811X (ISSN-L)
- PMC
- PMC12020182
- OpenAlex
- W4409738281
- Semantic Scholar
- 567ae7762d7013a795c77e80c80ed974b6ab577c
- Cited by
- 8
- References
- 88
- Citations by year
- 2026: 6 · 2025: 2
- FWCI
- 2.97
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Cell Communication and Signaling (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Charité - Universitätsmedizin Berlin
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Keywords
- TLR7, TLR8, Alzheimer's disease, neurodegenerative diseases, cortical neurons, synaptic proteins, neuronal viability, neuronal apoptosis, neuronal inflammation, miR-9-5p, miR-501-3p, microglia, cerebrospinal fluid, iPSC-derived neurons, intrathecal administration
- MeSH terms
- Alzheimer Disease, Animals, Cell Survival, Central Nervous System, Humans, Neurons, Signal Transduction, Microglia, Neurodegenerative Diseases, MicroRNAs, Toll-Like Receptor 7, Toll-Like Receptor 8, Mice, HEK293 Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
