{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T01:38:16Z","timestamp":1791509896951,"version":"4.3.4"},"reference-count":235,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,11,20]],"date-time":"2021-11-20T00:00:00Z","timestamp":1637366400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-10-IDEX-0002-02, ANR-10-LABX-0030-INRT, ANR-10-INBS-07 PHENOMIN"],"award-info":[{"award-number":["ANR-10-IDEX-0002-02, ANR-10-LABX-0030-INRT, ANR-10-INBS-07 PHENOMIN"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"name":"J\u00e9r\u00f4me Lejeune fondation","award":["to YH"],"award-info":[{"award-number":["to YH"]}]},{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"publisher","award":["H2020 GO-DS21 No 848077"],"award-info":[{"award-number":["H2020 GO-DS21 No 848077"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Down syndrome is the main cause of intellectual disabilities with a large set of comorbidities from developmental origins but also that appeared across life span. Investigation of the genetic overdosage found in Down syndrome, due to the trisomy of human chromosome 21, has pointed to one main driver gene, the Dual-specificity tyrosine-regulated kinase 1A (Dyrk1a). Dyrk1a is a murine homolog of the drosophila minibrain gene. It has been found to be involved in many biological processes during development and in adulthood. Further analysis showed its haploinsufficiency in mental retardation disease 7 and its involvement in Alzheimer\u2019s disease. DYRK1A plays a role in major developmental steps of brain development, controlling the proliferation of neural progenitors, the migration of neurons, their dendritogenesis and the function of the synapse. Several strategies targeting the overdosage of DYRK1A in DS with specific kinase inhibitors have showed promising evidence that DS cognitive conditions can be alleviated. Nevertheless, providing conditions for proper temporal treatment and to tackle the neurodevelopmental and the neurodegenerative aspects of DS across life span is still an open question.<\/jats:p>","DOI":"10.3390\/genes12111833","type":"journal-article","created":{"date-parts":[[2021,11,21]],"date-time":"2021-11-21T20:58:21Z","timestamp":1637528301000},"page":"1833","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":82,"title":["Dyrk1a from Gene Function in Development and Physiology to Dosage Correction across Life Span in Down Syndrome"],"prefix":"10.3390","volume":"12","author":[{"given":"Helin","family":"Atas-Ozcan","sequence":"first","affiliation":[{"name":"Universit\u00e9 de Strasbourg, CNRS, INSERM, Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire (IGBMC), 1 rue Laurent Fries, 67404 Illkirch Graffenstaden, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1418-5849","authenticated-orcid":false,"given":"V\u00e9ronique","family":"Brault","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Strasbourg, CNRS, INSERM, Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire (IGBMC), 1 rue Laurent Fries, 67404 Illkirch Graffenstaden, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnaud","family":"Duchon","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Strasbourg, CNRS, INSERM, Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire (IGBMC), 1 rue Laurent Fries, 67404 Illkirch Graffenstaden, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7049-6900","authenticated-orcid":false,"given":"Yann","family":"Herault","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Strasbourg, CNRS, INSERM, Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire (IGBMC), 1 rue Laurent Fries, 67404 Illkirch Graffenstaden, France"},{"name":"Universit\u00e9 de Strasbourg, CNRS, INSERM, Celphedia, Phenomin-Institut Clinique de la Souris (ICS), 1 rue Laurent Fries, 67404 Illkirch Graffenstaden, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1016\/j.celrep.2013.03.027","article-title":"The protein interaction landscape of the human CMGC kinase group","volume":"3","author":"Varjosalo","year":"2013","journal-title":"Cell Rep."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1101\/gad.3.9.1336","article-title":"Loss of Ras activity in Saccharomyces cerevisiae is suppressed by disruptions of a new kinase gene, YAKI, whose product may act downstream of the cAMP-dependent protein kinase","volume":"3","author":"Garrett","year":"1989","journal-title":"Genes Dev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/0896-6273(95)90286-4","article-title":"minibrain: A new protein kinase family involved in postembryonic neurogenesis in Drosophila","volume":"14","author":"Tejedor","year":"1995","journal-title":"Neuron"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"ra16","DOI":"10.1126\/scisignal.2000579","article-title":"Characterization of a domain that transiently converts class 2 DYRKs into intramolecular tyrosine kinases","volume":"3","author":"Kinstrie","year":"2010","journal-title":"Sci. Signal."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3099","DOI":"10.1242\/jcs.00618","article-title":"DYRK1A accumulates in splicing speckles through a novel targeting signal and induces speckle disassembly","volume":"116","author":"Alvarez","year":"2003","journal-title":"J. Cell Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1107\/S1399004715005106","article-title":"The structure of a dual-specificity tyrosine phosphorylation-regulated kinase 1A-PKC412 complex reveals disulfide-bridge formation with the anomalous catalytic loop HRD(HCD) cysteine","volume":"71","author":"Alexeeva","year":"2015","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"6610","DOI":"10.1016\/j.bmcl.2013.10.055","article-title":"Pyrido[2,3-d]pyrimidines: Discovery and preliminary SAR of a novel series of DYRK1B and DYRK1A inhibitors","volume":"23","author":"Anderson","year":"2013","journal-title":"Bioorgan. Med. Chem. Lett."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3131","DOI":"10.1021\/jm501994d","article-title":"10-iodo-11H-indolo[3,2-c]quinoline-6-carboxylic acids are selective inhibitors of DYRK1A","volume":"58","author":"Falke","year":"2015","journal-title":"J. Med. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1038\/ncomms1090","article-title":"Development of a novel selective inhibitor of the Down syndrome-related kinase Dyrk1A","volume":"1","author":"Ogawa","year":"2010","journal-title":"Nat. Commun."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"9312","DOI":"10.1021\/jm301034u","article-title":"Selectivity, cocrystal structures, and neuroprotective properties of leucettines, a family of protein kinase inhibitors derived from the marine sponge alkaloid leucettamine B","volume":"55","author":"Tahtouh","year":"2012","journal-title":"J. Med. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1016\/j.str.2013.03.012","article-title":"Structures of Down syndrome kinases, DYRKs, reveal mechanisms of kinase activation and substrate recognition","volume":"21","author":"Soundararajan","year":"2013","journal-title":"Structure"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"9814","DOI":"10.1021\/acs.jmedchem.6b01086","article-title":"Probing the ATP-Binding Pocket of Protein Kinase DYRK1A with Benzothiazole Fragment Molecules","volume":"59","author":"Rothweiler","year":"2016","journal-title":"J. Med. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1006\/geno.1999.5998","article-title":"High-level expression of the Mnb\/Dyrk1A gene in brain and heart during rat early development","volume":"62","author":"Okui","year":"1999","journal-title":"Genomics"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1006\/bbrc.1998.9803","article-title":"Expression of the mnb (dyrk) protein in adult and embryonic mouse tissues","volume":"253","author":"Rahmani","year":"1998","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1006\/geno.1999.5775","article-title":"Human minibrain homologue (MNBH\/DYRK1): Characterization, alternative splicing, differential tissue expression, and overexpression in Down syndrome","volume":"57","author":"Guimera","year":"1999","journal-title":"Genomics"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1093\/hmg\/5.9.1305","article-title":"A human homologue of Drosophila minibrain (MNB) is expressed in the neuronal regions affected in Down syndrome and maps to the critical region","volume":"5","author":"Casas","year":"1996","journal-title":"Hum. Meol. Gnet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1038\/mp.2015.5","article-title":"Disruptive de novo mutations of DYRK1A lead to a syndromic form of autism and ID","volume":"21","author":"Coe","year":"2016","journal-title":"Mol. Psychiatry"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1111\/j.1460-9568.2008.06092.x","article-title":"The spatio-temporal and subcellular expression of the candidate Down syndrome gene Mnb\/Dyrk1A in the developing mouse brain suggests distinct sequential roles in neuronal development","volume":"27","author":"Elizalde","year":"2008","journal-title":"Eur. J. Neurosci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2277","DOI":"10.1046\/j.1460-9568.2003.02665.x","article-title":"Expression patterns and subcellular localization of the Down syndrome candidate protein MNB\/DYRK1A suggest a role in late neuronal differentiation","volume":"17","author":"Hammerle","year":"2003","journal-title":"Eur. J. Neurosci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/S0006-8993(02)04069-6","article-title":"Dyrk1A expression pattern supports specific roles of this kinase in the adult central nervous system","volume":"964","author":"Marti","year":"2003","journal-title":"Brain Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.brainres.2004.03.008","article-title":"Cell type- and brain structure-specific patterns of distribution of minibrain kinase in human brain","volume":"1010","author":"Wegiel","year":"2004","journal-title":"Brain Res."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Maenz, B., Hekerman, P., Vela, E.M., Galceran, J., and Becker, W. (2008). Characterization of the human DYRK1A promoter and its regulation by the transcription factor E2F1. BMC Mol. Biol., 9.","DOI":"10.1186\/1471-2199-9-30"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"10755","DOI":"10.1074\/jbc.M110.174540","article-title":"REST Regulates DYRK1A Transcription in a Negative Feedback Loop","volume":"286","author":"Lu","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.nbd.2015.02.021","article-title":"Disruption of neurogenesis and cortical development in transgenic mice misexpressing Olig2, a gene in the Down syndrome critical region","volume":"77","author":"Liu","year":"2015","journal-title":"Neurobiol. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1038\/nn.2600","article-title":"Olig1 and Olig2 triplication causes developmental brain defects in Down syndrome","volume":"13","author":"Chakrabarti","year":"2010","journal-title":"Nat. Neurosci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1016\/j.neuron.2017.06.048","article-title":"A Requirement for Mena, an Actin Regulator, in Local mRNA Translation in Developing Neurons","volume":"95","author":"Vidaki","year":"2017","journal-title":"Neuron"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1101\/gad.1162404","article-title":"Modulation of mammalian life span by the short isoform of p53","volume":"18","author":"Maier","year":"2004","journal-title":"Genes Dev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1111\/j.1474-9726.2010.00547.x","article-title":"Altered longevity-assurance activity of p53:p44 in the mouse causes memory loss, neurodegeneration and premature death","volume":"9","author":"Pehar","year":"2010","journal-title":"Aging Cell"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1111\/acel.12192","article-title":"P44, the \u2018longevity-assurance\u2019 isoform of P53, regulates tau phosphorylation and is activated in an age-dependent fashion","volume":"13","author":"Pehar","year":"2014","journal-title":"Aging Cell"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"31895","DOI":"10.1074\/jbc.M110.147520","article-title":"Dyrk1A phosphorylates p53 and inhibits proliferation of embryonic neuronal cells","volume":"285","author":"Park","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1038\/embor.2011.98","article-title":"p53 downregulates Down syndrome-associated DYRK1A through miR-1246","volume":"12","author":"Zhang","year":"2011","journal-title":"EMBO Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1038\/ncb2126","article-title":"MicroRNA-199b targets the nuclear kinase Dyrk1a in an auto-amplification loop promoting calcineurin\/NFAT signalling","volume":"12","author":"Salic","year":"2010","journal-title":"Nat. Cell Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"399","DOI":"10.3389\/fncel.2019.00399","article-title":"Upregulated Expression of MicroRNA-204-5p Leads to the Death of Dopaminergic Cells by Targeting DYRK1A-Mediated Apoptotic Signaling Cascade","volume":"13","author":"Chiu","year":"2019","journal-title":"Front. Cell Neurosci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"6324","DOI":"10.1111\/j.1742-4658.2009.07346.x","article-title":"Harmine specifically inhibits protein kinase DYRK1A and interferes with neurite formation","volume":"276","author":"Jofre","year":"2009","journal-title":"FEBS J."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1042\/bj3590497","article-title":"Identification of the autophosphorylation sites and characterization of their effects in the protein kinase DYRK1A","volume":"359","author":"Himpel","year":"2001","journal-title":"Biochem. J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"7614","DOI":"10.1021\/bi700251n","article-title":"Dual-specificity tyrosine phosphorylation-regulated kinase 1A does not require tyrosine phosphorylation for activity in vitro","volume":"46","author":"Adayev","year":"2007","journal-title":"Biochemistry"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1016\/j.cell.2005.03.034","article-title":"Activation-loop autophosphorylation is mediated by a novel transitional intermediate form of DYRKs","volume":"121","author":"Lochhead","year":"2005","journal-title":"Cell"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"4495","DOI":"10.1111\/febs.12411","article-title":"Mechanism of dual specificity kinase activity of DYRK1A","volume":"280","author":"Walte","year":"2013","journal-title":"FEBS J."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"11391","DOI":"10.1038\/ncomms11391","article-title":"Selective inhibition of the kinase DYRK1A by targeting its folding process","volume":"7","author":"Kii","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1091\/mbc.e06-08-0668","article-title":"DYRK1A autophosphorylation on serine residue 520 modulates its kinase activity via 14-3-3 binding","volume":"18","author":"Alvarez","year":"2007","journal-title":"Mol. Biol. Cell"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3235","DOI":"10.1007\/s00018-009-0123-2","article-title":"Function and regulation of Dyrk1A: Towards understanding Down syndrome","volume":"66","author":"Park","year":"2009","journal-title":"Cell Mol. Life Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.neuroscience.2011.08.028","article-title":"Form of dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 1A nonphosphorylated at tyrosine 145 and 147 is enriched in the nuclei of astroglial cells, adult hippocampal progenitors, and some cholinergic axon terminals","volume":"195","author":"Kida","year":"2011","journal-title":"Neuroscience"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"35374","DOI":"10.1074\/jbc.M110.148445","article-title":"Direct association of Sprouty-related protein with an EVH1 domain (SPRED) 1 or SPRED2 with DYRK1A modifies substrate\/kinase interactions","volume":"285","author":"Li","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"39819","DOI":"10.1074\/jbc.M104091200","article-title":"Protein kinase Dyrk1 activates cAMP response element-binding protein during neuronal differentiation in hippocampal progenitor cells","volume":"276","author":"Yang","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1101\/gad.2000211","article-title":"A kinase shRNA screen links LATS2 and the pRB tumor suppressor","volume":"25","author":"Conery","year":"2011","journal-title":"Genes Dev."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"100245","DOI":"10.1074\/jbc.RA120.015574","article-title":"Protein phosphatase PPM1B inhibits DYRK1A kinase through dephosphorylation of pS258 and reduces toxic tau aggregation","volume":"296","author":"Lee","year":"2021","journal-title":"J. Biol. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"15219","DOI":"10.1074\/jbc.M115.645507","article-title":"Truncation and Activation of Dual Specificity Tyrosine Phosphorylation-regulated Kinase 1A by Calpain I: A molecular mechanism linked to tau pathology in Alzheimer disease","volume":"290","author":"Jin","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1186\/s40478-019-0678-6","article-title":"Inhibition of DYRK1A proteolysis modifies its kinase specificity and rescues Alzheimer phenotype in APP\/PS1 mice","volume":"7","author":"Souchet","year":"2019","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"26399","DOI":"10.1074\/jbc.M116.717553","article-title":"E3 Ligase SCF\u03b2TrCP-induced DYRK1A Protein Degradation Is Essential for Cell Cycle Progression in HEK293 Cells","volume":"291","author":"Liu","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"25893","DOI":"10.1074\/jbc.273.40.25893","article-title":"Sequence characteristics, subcellular localization, and substrate specificity of DYRK-related kinases, a novel family of dual specificity protein kinases","volume":"273","author":"Becker","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"5899","DOI":"10.1128\/MCB.00394-08","article-title":"Sprouty2-mediated inhibition of fibroblast growth factor signaling is modulated by the protein kinase DYRK1A","volume":"28","author":"Aranda","year":"2008","journal-title":"Mol. Cell Biol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Nguyen, T.L., Duchon, A., Manousopoulou, A., Loa\u00ebc, N., Villiers, B., Pani, G., Karatas, M., Mechling, A.E., Harsan, L.A., and Limanton, E. (2018). Correction of cognitive deficits in mouse models of Down syndrome by a pharmacological inhibitor of DYRK1A. Dis. Models Mech., 11.","DOI":"10.1242\/dmm.035634"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"33320","DOI":"10.1074\/jbc.M114.586115","article-title":"The molecular chaperone TRiC\/CCT binds to the Trp-Asp 40 (WD40) repeat protein WDR68 and promotes its folding, protein kinase DYRK1A binding, and nuclear accumulation","volume":"289","author":"Miyata","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.1016\/j.bbamcr.2011.06.023","article-title":"DYRK1A binds to an evolutionarily conserved WD40-repeat protein WDR68 and induces its nuclear translocation","volume":"1813","author":"Miyata","year":"2011","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/j.biocel.2004.12.006","article-title":"Dual-specificity tyrosine-phosphorylated and regulated kinase 1A (DYRK1A) interacts with the phytanoyl-CoA alpha-hydroxylase associated protein 1 (PAHX-AP1), a brain specific protein","volume":"37","author":"Bescond","year":"2005","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1002\/jnr.23279","article-title":"Intracellular distribution of differentially phosphorylated dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A)","volume":"92","author":"Kaczmarski","year":"2014","journal-title":"J. Neurosci. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1006\/geno.1995.1073","article-title":"Construction of a panel of transgenic mice containing a contiguous 2-Mb set of YAC\/P1 clones form human chromosome 21q22.2","volume":"27","author":"Smith","year":"1995","journal-title":"Genomics"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1915","DOI":"10.1093\/hmg\/10.18.1915","article-title":"Neurodevelopmental delay, motor abnormalities and cognitive deficits in transgenic mice overexpressing Dyrk1A (minibrain), a murine model of Down\u2019s syndrome","volume":"10","author":"Altafaj","year":"2001","journal-title":"Hum. Mol. Genet."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"6256","DOI":"10.1073\/pnas.95.11.6256","article-title":"Ts1Cje, a partial trisomy 16 mouse model for Down syndrome, exhibits learning and behavioral abnormalities","volume":"95","author":"Sago","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.nbd.2019.02.022","article-title":"Impaired development of neocortical circuits contributes to the neurological alterations in DYRK1A haploinsufficiency syndrome","volume":"127","author":"Arranz","year":"2019","journal-title":"Neurobiol. Dis."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"5821","DOI":"10.1128\/MCB.24.13.5821-5834.2004","article-title":"Dyrk1A potentiates steroid hormone-induced transcription via the chromatin remodeling factor Arip4","volume":"24","author":"Sitz","year":"2004","journal-title":"Mol. Cell Biol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.str.2015.10.020","article-title":"Structural Basis for the Non-catalytic Functions of Protein Kinases","volume":"24","author":"Kung","year":"2016","journal-title":"Structure"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2431","DOI":"10.1074\/jbc.275.4.2431","article-title":"Specificity determinants of substrate recognition by the protein kinase DYRK1A","volume":"275","author":"Himpel","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"34850","DOI":"10.1074\/jbc.M707358200","article-title":"DYRK1A-mediated hyperphosphorylation of Tau. A functional link between Down syndrome and Alzheimer disease","volume":"282","author":"Ryoo","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"3224","DOI":"10.1096\/fj.07-104539","article-title":"Overexpression of Dyrk1A contributes to neurofibrillary degeneration in Down syndrome","volume":"22","author":"Liu","year":"2008","journal-title":"FASEB J."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"23712","DOI":"10.1074\/jbc.M513497200","article-title":"Phosphorylation of amphiphysin I by minibrain kinase\/dual-specificity tyrosine phosphorylation-regulated kinase, a kinase implicated in Down syndrome","volume":"281","author":"Murakami","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1626","DOI":"10.1016\/j.cellsig.2009.06.009","article-title":"p38alpha- and DYRK1A-dependent phosphorylation of caspase-9 at an inhibitory site in response to hyperosmotic stress","volume":"21","author":"Seifert","year":"2009","journal-title":"Cell Signal."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"de Graaf, K., Czajkowska, H., Rottmann, S., Packman, L.C., Lilischkis, R., L\u00fcscher, B., and Becker, W. (2006). The protein kinase DYRK1A phosphorylates the splicing factor SF3b1\/SAP155 at Thr434, a novel in vivo phosphorylation site. BMC Biochem., 7.","DOI":"10.1186\/1471-2091-7-7"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"33250","DOI":"10.1074\/jbc.M606147200","article-title":"Dyrk1A phosphorylates alpha-synuclein and enhances intracellular inclusion formation","volume":"281","author":"Kim","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"3389","DOI":"10.4161\/cc.21404","article-title":"Emerging role of DYRK family protein kinases as regulators of protein stability in cell cycle control","volume":"11","author":"Becker","year":"2012","journal-title":"Cell Cycle"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1016\/j.ajhg.2008.03.001","article-title":"Truncation of the Down syndrome candidate gene DYRK1A in two unrelated patients with microcephaly","volume":"82","author":"Hoeltzenbein","year":"2008","journal-title":"Am. J. Hum. Genet."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1136\/jmedgenet-2012-101251","article-title":"The DYRK1A gene is a cause of syndromic intellectual disability with severe microcephaly and epilepsy","volume":"49","author":"Courcet","year":"2012","journal-title":"J. Med. Genet."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1111\/j.1399-0004.2010.01544.x","article-title":"Intragenic deletion in DYRK1A leads to mental retardation and primary microcephaly","volume":"79","author":"Hoischen","year":"2011","journal-title":"Clin. Genet."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"6636","DOI":"10.1128\/MCB.22.18.6636-6647.2002","article-title":"Dyrk1A haploinsufficiency affects viability and causes developmental delay and abnormal brain morphology in mice","volume":"22","author":"Fotaki","year":"2002","journal-title":"Mol. Cell Biol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1111\/j.1742-4658.2010.07954.x","article-title":"MNB\/DYRK1A as a multiple regulator of neuronal development","volume":"278","author":"Tejedor","year":"2011","journal-title":"FEBS J."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"4004","DOI":"10.1523\/JNEUROSCI.4711-09.2010","article-title":"Dyrk1A overexpression inhibits proliferation and induces premature neuronal differentiation of neural progenitor cells","volume":"30","author":"Yabut","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1002\/hipo.20308","article-title":"Cell cycle alteration and decreased cell proliferation in the hippocampal dentate gyrus and in the neocortical germinal matrix of fetuses with Down syndrome and in Ts65Dn mice","volume":"17","author":"Contestabile","year":"2007","journal-title":"Hippocampus"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.aanat.2008.05.007","article-title":"Reduced cell number in the neocortical part of the human fetal brain in Down syndrome","volume":"190","author":"Larsen","year":"2008","journal-title":"Ann. Anat."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2543","DOI":"10.1242\/dev.066167","article-title":"Transient expression of Mnb\/Dyrk1a couples cell cycle exit and differentiation of neuronal precursors by inducing p27KIP1 expression and suppressing NOTCH signaling","volume":"138","author":"Ulin","year":"2011","journal-title":"Development"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2084","DOI":"10.4161\/cc.29104","article-title":"The Down syndrome-related protein kinase DYRK1A phosphorylates p27(Kip1) and Cyclin D1 and induces cell cycle exit and neuronal differentiation","volume":"13","author":"Soppa","year":"2014","journal-title":"Cell Cycle"},{"key":"ref_81","first-page":"3195","article-title":"Minibrain drives the Dacapo-dependent cell cycle exit of neurons in the Drosophila brain by promoting asense and prospero expression","volume":"143","author":"Shaikh","year":"2016","journal-title":"Development"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.molcel.2013.09.009","article-title":"Dosage of Dyrk1a shifts cells within a p21-cyclin D1 signaling map to control the decision to enter the cell cycle","volume":"52","author":"Chen","year":"2013","journal-title":"Mol. Cell"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1101\/gad.2034211","article-title":"DYRK1A protein kinase promotes quiescence and senescence through DREAM complex assembly","volume":"25","author":"Litovchick","year":"2011","journal-title":"Genes Dev."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.biopsych.2021.01.012","article-title":"Dyrk1a Mutations Cause Undergrowth of Cortical Pyramidal Neurons via Dysregulated Growth Factor Signaling","volume":"90","author":"Levy","year":"2021","journal-title":"Biol. Psychiatry"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.ebiom.2015.01.010","article-title":"DYRK1A-mediated Cyclin D1 Degradation in Neural Stem Cells Contributes to the Neurogenic Cortical Defects in Down Syndrome","volume":"2","author":"Najas","year":"2015","journal-title":"EBioMedicine"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"4612","DOI":"10.1074\/jbc.M310794200","article-title":"Characterization of cyclin L2, a novel cyclin with an arginine\/serine-rich domain: Phosphorylation by DYRK1A and colocalization with splicing factors","volume":"279","author":"Hekerman","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1042\/BJ20060159","article-title":"dDYRK2 and Minibrain interact with the chromatin remodelling factors SNR1 and TRX","volume":"398","author":"Kinstrie","year":"2006","journal-title":"Biochem. J."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"3562","DOI":"10.1091\/mbc.e04-12-1085","article-title":"DYRK1A enhances the mitogen-activated protein kinase cascade in PC12 cells by forming a complex with Ras, B-Raf, and MEK1","volume":"16","author":"Kelly","year":"2005","journal-title":"Mol. Biol. Cell"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"35156","DOI":"10.1074\/jbc.M206743200","article-title":"Regulation of Gli1 transcriptional activity in the nucleus by Dyrk1","volume":"277","author":"Mao","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1016\/j.bbrc.2017.07.107","article-title":"Identification of a DYRK1A-mediated phosphorylation site within the nuclear localization sequence of the hedgehog transcription factor GLI1","volume":"491","author":"Ehe","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1574","DOI":"10.1242\/jcs.044354","article-title":"Attenuation of Notch signalling by the Down-syndrome-associated kinase DYRK1A","volume":"122","author":"Vela","year":"2009","journal-title":"J. Cell Sci."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2490","DOI":"10.1074\/jbc.M301769200","article-title":"Phosphorylation of Ser640 in muscle glycogen synthase by DYRK family protein kinases","volume":"279","author":"Skurat","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1042\/bj3550597","article-title":"The kinase DYRK1A phosphorylates the transcription factor FKHR at Ser329 in vitro, a novel in vivo phosphorylation site","volume":"355","author":"Woods","year":"2001","journal-title":"Biochem. J."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2424","DOI":"10.1242\/jcs.040162","article-title":"Nonprimed and DYRK1A-primed GSK3 beta-phosphorylation sites on MAP1B regulate microtubule dynamics in growing axons","volume":"122","author":"Scales","year":"2009","journal-title":"J. Cell Sci."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/j.cub.2008.02.005","article-title":"Pom1 DYRK regulates localization of the Rga4 GAP to ensure bipolar activation of Cdc42 in fission yeast","volume":"18","author":"Tatebe","year":"2008","journal-title":"Curr. Biol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1242\/jcs.086124","article-title":"Dyrk1A negatively regulates the actin cytoskeleton through threonine phosphorylation of N-WASP","volume":"125","author":"Park","year":"2012","journal-title":"J. Cell Sci."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1007\/s12035-012-8326-1","article-title":"Dyrk1A, a serine\/threonine kinase, is involved in ERK and Akt activation in the brain of hyperhomocysteinemic mice","volume":"47","author":"Abekhoukh","year":"2013","journal-title":"Mol. Neurobiol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1002\/hipo.20351","article-title":"Dysregulation of growth factor receptor-bound protein 2 and fascin in hippocampus of mice polytransgenic for chromosome 21 structures","volume":"17","author":"Shin","year":"2007","journal-title":"Hippocampus"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"6","DOI":"10.5483\/BMBRep.2009.42.1.006","article-title":"Two key genes closely implicated with the neuropathological characteristics in Down syndrome: DYRK1A and RCAN1","volume":"42","author":"Park","year":"2009","journal-title":"BMB Rep."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1038\/nature04631","article-title":"A genome-wide Drosophila RNAi screen identifies DYRK-family kinases as regulators of NFAT","volume":"441","author":"Gwack","year":"2006","journal-title":"Nature"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1038\/nature04678","article-title":"NFAT dysregulation by increased dosage of DSCR1 and DYRK1A on chromosome 21","volume":"441","author":"Arron","year":"2006","journal-title":"Nature"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"33343","DOI":"10.1074\/jbc.M109.042234","article-title":"Negative feedback Inhibition of NFATc1 by DYRK1A regulates bone homeostasis","volume":"284","author":"Lee","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.neulet.2013.08.066","article-title":"Dyrk1A-mediated phosphorylation of RCAN1 promotes the formation of insoluble RCAN1 aggregates","volume":"554","author":"Song","year":"2013","journal-title":"Neurosci. Lett."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"40401","DOI":"10.1074\/jbc.M111.253971","article-title":"Regulation of RCAN1 protein activity by Dyrk1A protein-mediated phosphorylation","volume":"286","author":"Jung","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1016\/j.molcel.2014.12.026","article-title":"Chromatin-wide profiling of DYRK1A reveals a role as a gene-specific RNA polymerase II CTD kinase","volume":"57","author":"Bezdan","year":"2015","journal-title":"Mol. Cell"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"17597","DOI":"10.1074\/jbc.M111101200","article-title":"Dynamin is a minibrain kinase\/dual specificity Yak1-related kinase 1A substrate","volume":"277","author":"Chen","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Murakami, N., Bolton, D.C., Kida, E., Xie, W., and Hwang, Y.W. (2012). Phosphorylation by Dyrk1A of clathrin coated vesicle-associated proteins: Identification of the substrate proteins and the effects of phosphorylation. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0034845"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"10173","DOI":"10.1021\/bi036060+","article-title":"Mnb\/Dyrk1A phosphorylation regulates the interaction of dynamin 1 with SH3 domain-containing proteins","volume":"43","author":"Huang","year":"2004","journal-title":"Biochemistry"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"9297","DOI":"10.1021\/bi9010557","article-title":"Dyrk1A binds to multiple endocytic proteins required for formation of clathrin-coated vesicles","volume":"48","author":"Murakami","year":"2009","journal-title":"Biochemistry"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1016\/j.bbrc.2006.10.169","article-title":"MNB\/DYRK1A phosphorylation regulates the interactions of synaptojanin 1 with endocytic accessory proteins","volume":"351","author":"Adayev","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"4246","DOI":"10.1038\/ncomms5246","article-title":"Activity-dependent facilitation of Synaptojanin and synaptic vesicle recycling by the Minibrain kinase","volume":"5","author":"Chen","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"2321","DOI":"10.1074\/jbc.M114.594952","article-title":"Phosphorylation and inactivation of glycogen synthase kinase 3\u03b2 (GSK3\u03b2) by dual-specificity tyrosine phosphorylation-regulated kinase 1A (Dyrk1A)","volume":"290","author":"Song","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/j.neuron.2016.03.027","article-title":"Phosphorylation of \u03b2-Tubulin by the Down Syndrome Kinase, Minibrain\/DYRK1a, Regulates Microtubule Dynamics and Dendrite Morphogenesis","volume":"90","author":"McKenney","year":"2016","journal-title":"Neuron"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1111\/j.1471-4159.2012.07861.x","article-title":"Phosphorylation of Munc18-1 by Dyrk1A regulates its interaction with Syntaxin 1 and X11\u03b1","volume":"122","author":"Park","year":"2012","journal-title":"J. Neurochem."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.nbd.2008.07.024","article-title":"Increased NR2A expression and prolonged decay of NMDA-induced calcium transient in cerebellum of TgDyrk1A mice, a mouse model of Down syndrome","volume":"32","author":"Altafaj","year":"2008","journal-title":"Neurobiol. Dis."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"331","DOI":"10.3389\/fncel.2014.00331","article-title":"DYRK1A-mediated phosphorylation of GluN2A at Ser(1048) regulates the surface expression and channel activity of GluN1\/GluN2A receptors","volume":"8","author":"Grau","year":"2014","journal-title":"Front. Cell Neurosci."},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Brault, V., Nguyen, T.L., Flores-Guti\u00e9rrez, J., Iacono, G., Birling, M.C., Lalanne, V., Meziane, H., Manousopoulou, A., Pavlovic, G., and Lindner, L. (2021). Dyrk1a gene dosage in glutamatergic neurons has key effects in cognitive deficits observed in mouse models of MRD7 and Down syndrome. PLoS Genet., 17.","DOI":"10.1101\/2021.05.01.442242"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.nbd.2014.04.016","article-title":"Excitation\/inhibition balance and learning are modified by Dyrk1a gene dosage","volume":"69","author":"Souchet","year":"2014","journal-title":"Neurobiol. Dis."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1093\/hmg\/ddp047","article-title":"DYRK1A interacts with the REST\/NRSF-SWI\/SNF chromatin remodelling complex to deregulate gene clusters involved in the neuronal phenotypic traits of Down syndrome","volume":"18","author":"Zvara","year":"2009","journal-title":"Hum. Mol. Genet."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"686","DOI":"10.15252\/embr.201338356","article-title":"DYRK1A phoshorylates histone H3 to differentially regulate the binding of HP1 isoforms and antagonize HP1-mediated transcriptional repression","volume":"15","author":"Jang","year":"2014","journal-title":"EMBO Rep."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"28660","DOI":"10.1074\/jbc.M802645200","article-title":"Increased dosage of Dyrk1A alters alternative splicing factor (ASF)-regulated alternative splicing of tau in Down syndrome","volume":"283","author":"Shi","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1016\/j.neurobiolaging.2010.11.021","article-title":"Regulation of alternative splicing of tau exon 10 by 9G8 and Dyrk1A","volume":"33","author":"Ding","year":"2012","journal-title":"Neurobiol. Aging"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"6161","DOI":"10.1093\/nar\/gkr195","article-title":"Regulation of the alternative splicing of tau exon 10 by SC35 and Dyrk1A","volume":"39","author":"Qian","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"30497","DOI":"10.1074\/jbc.M112.355412","article-title":"Dual-specificity tyrosine phosphorylation-regulated kinase 1A (Dyrk1A) modulates serine\/arginine-rich protein 55 (SRp55)-promoted Tau exon 10 inclusion","volume":"287","author":"Yin","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"6539","DOI":"10.1038\/s41598-019-42990-5","article-title":"The nuclear interactome of DYRK1A reveals a functional role in DNA damage repair","volume":"9","author":"Guard","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1080\/15384101.2019.1577525","article-title":"DYRK1A regulates the recruitment of 53BP1 to the sites of DNA damage in part through interaction with RNF169","volume":"18","author":"Menon","year":"2019","journal-title":"Cell Cycle"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"6014","DOI":"10.1038\/s41598-019-42445-x","article-title":"A comprehensive proteomics-based interaction screen that links DYRK1A to RNF169 and to the DNA damage response","volume":"9","author":"Roewenstrunk","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1042\/bj3550609","article-title":"The kinase DYRK phosphorylates protein-synthesis initiation factor eIF2Bepsilon at Ser539 and the microtubule-associated protein tau at Thr212: Potential role for DYRK as a glycogen synthase kinase 3-priming kinase","volume":"355","author":"Woods","year":"2001","journal-title":"Biochem. J."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.mcn.2007.07.007","article-title":"Dyrk1A overexpression in immortalized hippocampal cells produces the neuropathological features of Down syndrome","volume":"36","author":"Park","year":"2007","journal-title":"Mol. Cell Neurosci."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1111\/j.1471-4159.2007.05075.x","article-title":"Dual-specificity tyrosine(Y)-phosphorylation regulated kinase 1A-mediated phosphorylation of amyloid precursor protein: Evidence for a functional link between Down syndrome and Alzheimer\u2019s disease","volume":"104","author":"Ryoo","year":"2008","journal-title":"J. Neurochem."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/j.nbd.2005.05.004","article-title":"Phosphorylation of amyloid precursor carboxy-terminal fragments enhances their processing by a gamma-secretase-dependent mechanism","volume":"20","author":"Vingtdeux","year":"2005","journal-title":"Neurobiol. Dis."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"6268","DOI":"10.1111\/j.1742-4658.2008.06751.x","article-title":"DYRK1A phosphorylates caspase 9 at an inhibitory site and is potently inhibited in human cells by harmine","volume":"275","author":"Seifert","year":"2008","journal-title":"FEBS J."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1016\/j.devcel.2008.10.014","article-title":"The protein kinase DYRK1A regulates caspase-9-mediated apoptosis during retina development","volume":"15","author":"Laguna","year":"2008","journal-title":"Dev. Cell"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"699","DOI":"10.3233\/JPD-150642","article-title":"The Synaptic Function of \u03b1-Synuclein","volume":"5","year":"2015","journal-title":"J. Parkinson\u2019s Dis."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"13223","DOI":"10.1074\/jbc.M110.102574","article-title":"DYRK1A and DYRK3 promote cell survival through phosphorylation and activation of SIRT1","volume":"285","author":"Guo","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1016\/j.neuroscience.2008.09.034","article-title":"The Down syndrome candidate dual-specificity tyrosine phosphorylation-regulated kinase 1A phosphorylates the neurodegeneration-related septin 4","volume":"157","author":"Sitz","year":"2008","journal-title":"Neuroscience"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1111\/j.1471-4159.2010.06769.x","article-title":"Dyrk1A-mediated phosphorylation of Presenilin 1: A functional link between Down syndrome and Alzheimer\u2019s disease","volume":"115","author":"Ryu","year":"2010","journal-title":"J. Neurochem."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1248\/yakushi.16-00236-2","article-title":"Elucidating Pathogenic Mechanisms of Early-onset Alzheimer\u2019s Disease in Down Syndrome Patients","volume":"137","author":"Asai","year":"2017","journal-title":"Yakugaku Zasshi"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1248\/bpb.b16-00825","article-title":"Neprilysin Is Suppressed by Dual-Specificity Tyrosine-Phosphorylation Regulated Kinase 1A (DYRK1A) in Down-Syndrome-Derived Fibroblasts","volume":"40","author":"Kawakubo","year":"2017","journal-title":"Biol. Pharm. Bull."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1002\/hipo.22832","article-title":"CA1 pyramidal neuron gene expression mosaics in the Ts65Dn murine model of Down syndrome and Alzheimer\u2019s disease following maternal choline supplementation","volume":"28","author":"Alldred","year":"2018","journal-title":"Hippocampus"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1111\/jnc.13164","article-title":"Dyrk1A phosphorylates parkin at Ser-131 and negatively regulates its ubiquitin E3 ligase activity","volume":"134","author":"Im","year":"2015","journal-title":"J. Neurochem."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1002\/jnr.20534","article-title":"Regulation of the proapoptotic activity of huntingtin interacting protein 1 by Dyrk1 and caspase-3 in hippocampal neuroprogenitor cells","volume":"81","author":"Kang","year":"2005","journal-title":"J. Neurosci. Res."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"E1224","DOI":"10.1073\/pnas.1614893114","article-title":"DYRK1A regulates Hap1-Dcaf7\/WDR68 binding with implication for delayed growth in Down syndrome","volume":"114","author":"Xiang","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_144","doi-asserted-by":"crossref","unstructured":"Willsey, H.R., Xu, Y., Everitt, A., Dea, J., Exner, C.R.T., Willsey, A.J., State, M.W., and Harland, R.M. (2020). The neurodevelopmental disorder risk gene DYRK1A is required for ciliogenesis and control of brain size in Xenopus embryos. Development, 147.","DOI":"10.1242\/dev.198317"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1007\/BF00688755","article-title":"Spine distribution along the apical dendrites of the pyramidal neurons in Down\u2019s syndrome. A quantitative Golgi study","volume":"50","author":"Suetsugu","year":"1980","journal-title":"Acta Neuropathol."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1007\/BF00294247","article-title":"Down\u2019s syndrome and Alzheimer\u2019s disease: Dendritic spine counts in the hippocampus","volume":"79","author":"Ferrer","year":"1990","journal-title":"Acta Neuropathol."},{"key":"ref_147","doi-asserted-by":"crossref","unstructured":"Haas, M.A., Bell, D., Slender, A., Lana-Elola, E., Watson-Scales, S., Fisher, E.M., Tybulewicz, V.L., and Guillemot, F. (2013). Alterations to dendritic spine morphology, but not dendrite patterning, of cortical projection neurons in Tc1 and Ts1Rhr mouse models of Down syndrome. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0078561"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"2867","DOI":"10.1093\/cercor\/bhr362","article-title":"Dyrk1A influences neuronal morphogenesis through regulation of cytoskeletal dynamics in mammalian cortical neurons","volume":"22","author":"Calvo","year":"2012","journal-title":"Cereb. Cortex"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.nbd.2005.02.004","article-title":"Alterations in the phenotype of neocortical pyramidal cells in the Dyrk1A+\/\u2212 mouse","volume":"20","author":"Dierssen","year":"2005","journal-title":"Neurobiol. Dis."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1038\/mp.2016.253","article-title":"Autism-associated Dyrk1a truncation mutants impair neuronal dendritic and spine growth and interfere with postnatal cortical development","volume":"23","author":"Dang","year":"2018","journal-title":"Mol. Psychiatry"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"R26","DOI":"10.1186\/gb-2009-10-3-r26","article-title":"Parallel RNAi screens across different cell lines identify generic and cell type-specific regulators of actin organization and cell morphology","volume":"10","author":"Liu","year":"2009","journal-title":"Genome Biol."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"8153","DOI":"10.1523\/JNEUROSCI.1766-04.2004","article-title":"Hippocampal long-term potentiation suppressed by increased inhibition in the Ts65Dn mouse, a genetic model of Down syndrome","volume":"24","author":"Kleschevnikov","year":"2004","journal-title":"J. Neurosci."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1016\/S0028-3908(99)00083-0","article-title":"Increased synaptic depression in the Ts65Dn mouse, a model for mental retardation in Down syndrome","volume":"38","author":"Siarey","year":"1999","journal-title":"Neuropharmacology"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1111\/j.1471-4159.2006.03971.x","article-title":"Altered signaling pathways underlying abnormal hippocampal synaptic plasticity in the Ts65Dn mouse model of Down syndrome","volume":"98","author":"Siarey","year":"2006","journal-title":"J. Neurochem."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"3953","DOI":"10.1523\/JNEUROSCI.1203-12.2013","article-title":"Reducing GABAA \u03b15 Receptor-Mediated Inhibition Rescues Functional and Neuromorphological Deficits in a Mouse Model of Down Syndrome","volume":"33","author":"Rueda","year":"2013","journal-title":"J. Neurosci."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.nbd.2015.07.014","article-title":"Early environmental therapy rescues brain development in a mouse model of Down syndrome","volume":"82","author":"Begenisic","year":"2015","journal-title":"Neurobiol. Dis."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/j.nbd.2015.09.005","article-title":"Rapamycin restores BDNF-LTP and the persistence of long-term memory in a model of Down\u2019s syndrome","volume":"82","author":"Benito","year":"2015","journal-title":"Neurobiol. Dis."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1523\/JNEUROSCI.2852-13.2014","article-title":"Prefrontal deficits in a murine model overexpressing the down syndrome candidate gene dyrk1a","volume":"34","author":"Thomazeau","year":"2014","journal-title":"J. Neurosci."},{"key":"ref_159","first-page":"153218","article-title":"Chronic Treatment with a Promnesiant GABA-A \u03b15-Selective Inverse Agonist Increases Immediate Early Genes Expression during Memory Processing in Mice and Rectifies Their Expression Levels in a Down Syndrome Mouse Model","volume":"2011","author":"Braudeau","year":"2011","journal-title":"Adv. Pharmacol. Sci."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1093\/hmg\/ddab012","article-title":"Multi-influential genetic interactions alter behaviour and cognition through six main biological cascades in Down syndrome mouse models","volume":"30","author":"Duchon","year":"2021","journal-title":"Hum. Mol. Genet."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"8378","DOI":"10.1523\/JNEUROSCI.0872-07.2007","article-title":"RhoA regulates dendrite branching in hippocampal neurons by decreasing cypin protein levels","volume":"27","author":"Chen","year":"2007","journal-title":"J. Neurosci."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1016\/j.neuron.2009.05.007","article-title":"Neural activity regulates synaptic properties and dendritic structure in vivo through calcineurin\/NFAT signaling","volume":"62","author":"Schwartz","year":"2009","journal-title":"Neuron"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.mcn.2010.12.010","article-title":"NFAT regulates pre-synaptic development and activity-dependent plasticity in Drosophila","volume":"46","author":"Freeman","year":"2011","journal-title":"Mol. Cell Neurosci."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1038\/s41593-018-0076-6","article-title":"Memory formation depends on both synapse-specific modifications of synaptic strength and cell-specific increases in excitability","volume":"21","author":"Lisman","year":"2018","journal-title":"Nat. Neurosci."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"8882","DOI":"10.1523\/JNEUROSCI.1470-16.2016","article-title":"Phosphorylation of Synaptojanin Differentially Regulates Endocytosis of Functionally Distinct Synaptic Vesicle Pools","volume":"36","author":"Geng","year":"2016","journal-title":"J. Neurosci."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1159\/000321994","article-title":"Overexpression of Dyrk1A Causes the Defects in Synaptic Vesicle Endocytosis","volume":"18","author":"Kim","year":"2010","journal-title":"Neurosignals"},{"key":"ref_167","doi-asserted-by":"crossref","unstructured":"Arque, G., Casanovas, A., and Dierssen, M. (2013). Dyrk1A is dynamically expressed on subsets of motor neurons and in the neuromuscular junction: Possible role in Down syndrome. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0054285"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1038\/nrn3983","article-title":"A genetic cause of Alzheimer disease: Mechanistic insights from Down syndrome","volume":"16","author":"Wiseman","year":"2015","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1007\/s11064-007-9497-4","article-title":"The place of choline acetyltransferase activity measurement in the \u201cCholinergic hypothesis\u201d of neurodegenerative diseases","volume":"33","author":"Contestabile","year":"2008","journal-title":"Neurochem. Res."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1006\/exnr.1999.7289","article-title":"Loss of cholinergic phenotype in basal forebrain coincides with cognitive decline in a mouse model of Down\u2019s syndrome","volume":"161","author":"Granholm","year":"2000","journal-title":"Exp. Neurol."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/S0168-0102(03)00005-1","article-title":"Regional alterations in amyloid precursor protein and nerve growth factor across age in a mouse model of Down\u2019s syndrome","volume":"45","author":"Hunter","year":"2003","journal-title":"Neurosci Res"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/j.expneurol.2004.11.017","article-title":"Abnormal APP, cholinergic and cognitive function in Ts65Dn Down\u2019s model mice","volume":"193","author":"Seo","year":"2005","journal-title":"Exp. Neurol."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"471","DOI":"10.3233\/JAD-2010-101218","article-title":"A noradrenergic lesion exacerbates neurodegeneration in a Down syndrome mouse model","volume":"23","author":"Lockrow","year":"2011","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"463909","DOI":"10.1155\/2012\/463909","article-title":"Age-related neurodegeneration and memory loss in down syndrome","volume":"2012","author":"Lockrow","year":"2012","journal-title":"Curr. Gerontol. Geriatr. Res."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.bbi.2018.10.004","article-title":"Restoring microglial and astroglial homeostasis using DNA immunization in a Down Syndrome mouse model","volume":"75","author":"Illouz","year":"2019","journal-title":"Brain Behav. Immun."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1111\/bpa.12073","article-title":"Sex differences in the cholinergic basal forebrain in the Ts65Dn mouse model of Down syndrome and Alzheimer\u2019s disease","volume":"24","author":"Kelley","year":"2014","journal-title":"Brain Pathol."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/S0006-8993(96)01173-0","article-title":"Alterations of central noradrenergic transmission in Ts65Dn mouse, a model for Down syndrome","volume":"749","author":"Dierssen","year":"1997","journal-title":"Brain Res."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1016\/j.neurobiolaging.2003.10.010","article-title":"Behavioral and neurobiological markers of Alzheimer\u2019s disease in Ts65Dn mice: Effects of estrogen","volume":"25","author":"Hunter","year":"2004","journal-title":"Neurobiol. Aging"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.brainres.2009.08.052","article-title":"Beta-amyloid overload does not directly correlate with SAPK\/JNK activation and tau protein phosphorylation in the cerebellar cortex of Ts65Dn mice","volume":"1297","author":"Lomoio","year":"2009","journal-title":"Brain Res."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.expneurol.2016.06.006","article-title":"Experience-dependent reduction of soluble \u03b2-amyloid oligomers and rescue of cognitive abilities in middle-age Ts65Dn mice, a model of Down syndrome","volume":"283","author":"Sansevero","year":"2016","journal-title":"Exp. Neurol."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.molcel.2006.03.009","article-title":"The apoptosome activates caspase-9 by dimerization","volume":"22","author":"Pop","year":"2006","journal-title":"Mol. Cell"},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1038\/ncb1005","article-title":"Inhibition of caspase-9 through phosphorylation at Thr 125 by ERK MAPK","volume":"5","author":"Allan","year":"2003","journal-title":"Nat. Cell Biol."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"10543","DOI":"10.1128\/MCB.25.23.10543-10555.2005","article-title":"Regulation of caspase 9 through phosphorylation by protein kinase C zeta in response to hyperosmotic stress","volume":"25","author":"Brady","year":"2005","journal-title":"Mol. Cell Biol."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"15449","DOI":"10.1074\/jbc.M414325200","article-title":"Protein kinase A regulates caspase-9 activation by Apaf-1 downstream of cytochrome c","volume":"280","author":"Martin","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1146\/annurev.cellbio.15.1.269","article-title":"Biochemical pathways of caspase activation during apoptosis","volume":"15","author":"Budihardjo","year":"1999","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1016\/j.nbd.2005.03.020","article-title":"Constitutive Dyrk1A is abnormally expressed in Alzheimer disease, Down syndrome, Pick disease, and related transgenic models","volume":"20","author":"Ferrer","year":"2005","journal-title":"Neurobiol. Dis."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/hmg\/ddl437","article-title":"The DYRK1A gene, encoded in chromosome 21 Down syndrome critical region, bridges between beta-amyloid production and tau phosphorylation in Alzheimer disease","volume":"16","author":"Kimura","year":"2007","journal-title":"Hum. Mol. Genet."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1097\/NEN.0b013e318202bfa1","article-title":"Link between DYRK1A overexpression and several-fold enhancement of neurofibrillary degeneration with 3-repeat tau protein in Down syndrome","volume":"70","author":"Wegiel","year":"2011","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1111\/j.1742-4658.2010.07955.x","article-title":"The role of DYRK1A in neurodegenerative diseases","volume":"278","author":"Wegiel","year":"2011","journal-title":"FEBS J."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"244","DOI":"10.5607\/en.2013.22.4.244","article-title":"New Perspectives of Dyrk1A Role in Neurogenesis and Neuropathologic Features of Down Syndrome","volume":"22","author":"Park","year":"2013","journal-title":"Exp. Neurobiol."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1007\/s12035-018-1113-x","article-title":"LPS-Induced Inflammation Abolishes the Effect of DYRK1A on IkB Stability in the Brain of Mice","volume":"56","author":"Latour","year":"2019","journal-title":"Mol. Neurobiol."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1242\/dmm.029728","article-title":"Rodent models in Down syndrome research: Impact and future opportunities","volume":"10","author":"Herault","year":"2017","journal-title":"Dis. Models Mech."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"104","DOI":"10.3389\/fnbeh.2016.00104","article-title":"DYRK1A, a Dosage-Sensitive Gene Involved in Neurodevelopmental Disorders, Is a Target for Drug Development in Down Syndrome","volume":"10","author":"Duchon","year":"2016","journal-title":"Front. Behav. Neurosci."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/j.ajhg.2008.09.010","article-title":"Targeting Dyrk1A with AAVshRNA attenuates motor alterations in TgDyrk1A, a mouse model of Down syndrome","volume":"83","author":"Altafaj","year":"2008","journal-title":"Am. J. Hum. Genet."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.nbd.2017.06.010","article-title":"Normalizing the gene dosage of Dyrk1A in a mouse model of Down syndrome rescues several Alzheimer\u2019s disease phenotypes","volume":"106","author":"Rueda","year":"2017","journal-title":"Neurobiol. Dis."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.nbd.2012.11.017","article-title":"Normalization of Dyrk1A expression by AAV2\/1-shDyrk1A attenuates hippocampal-dependent defects in the Ts65Dn mouse model of Down syndrome","volume":"52","author":"Altafaj","year":"2013","journal-title":"Neurobiol. Dis."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1002\/mnfr.201300325","article-title":"Epigallocatechin-3-gallate, a DYRK1A inhibitor, rescues cognitive deficits in Down syndrome mouse models and in humans","volume":"58","author":"Pons","year":"2014","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_198","doi-asserted-by":"crossref","unstructured":"Guedj, F., S\u00e9bri\u00e9, C., Rivals, I., Ledru, A., Paly, E., Bizot, J.C., Smith, D., Rubin, E., Gillet, B., and Arbones, M. (2009). Green tea polyphenols rescue of brain defects induced by overexpression of DYRK1A. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0004606"},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1016\/j.ymgme.2011.11.194","article-title":"Dyrk1a activates antioxidant NQO1 expression through an ERK1\/2-Nrf2 dependent mechanism","volume":"105","author":"Noll","year":"2012","journal-title":"Mol. Genet. Metab."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1016\/S1474-4422(16)30034-5","article-title":"Safety and efficacy of cognitive training plus epigallocatechin-3-gallate in young adults with Down\u2019s syndrome (TESDAD): A double-blind, randomised, placebo-controlled, phase 2 trial","volume":"15","author":"Hernandez","year":"2016","journal-title":"Lancet Neurol."},{"key":"ref_201","first-page":"839","article-title":"A chemical with proven clinical safety rescues Down-syndrome-related phenotypes in through DYRK1A inhibition","volume":"9","author":"Kim","year":"2016","journal-title":"Dis. Models Mech."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"2859","DOI":"10.1038\/s41598-018-20984-z","article-title":"DYRK1A inhibition and cognitive rescue in a Down syndrome mouse model are induced by new fluoro-DANDY derivatives","volume":"8","author":"Neumann","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1042\/BJ20070797","article-title":"The selectivity of protein kinase inhibitors: A further update","volume":"408","author":"Bain","year":"2007","journal-title":"Biochem. J."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.nbd.2012.01.007","article-title":"DYRK1A: A master regulatory protein controlling brain growth","volume":"46","author":"Guedj","year":"2012","journal-title":"Neurobiol. Dis."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1038\/ng1095-177","article-title":"A mouse model for Down syndrome exhibits learning and behaviour deficits","volume":"11","author":"Reeves","year":"1995","journal-title":"Nat. Genet."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1007\/s00335-011-9356-0","article-title":"Identification of the translocation breakpoints in the Ts65Dn and Ts1Cje mouse lines: Relevance for modeling Down syndrome","volume":"22","author":"Duchon","year":"2011","journal-title":"Mamm. Genome"},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1002\/jnr.23007","article-title":"Effect of DYRK1A activity inhibition on development of neuronal progenitors isolated from Ts65Dn mice","volume":"90","author":"Golabek","year":"2012","journal-title":"J. Neurosci. Res."},{"key":"ref_208","doi-asserted-by":"crossref","unstructured":"Frost, D., Meechoovet, B., Wang, T., Gately, S., Giorgetti, M., Shcherbakova, I., and Dunckley, T. (2011). \u03b2-carboline compounds, including harmine, inhibit DYRK1A and tau phosphorylation at multiple Alzheimer\u2019s disease-related sites. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0019264"},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1006\/abbi.1996.9771","article-title":"Inhibition of monoamine oxidase A by beta-carboline derivatives","volume":"337","author":"Kim","year":"1997","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"4854","DOI":"10.1016\/j.bmcl.2014.08.054","article-title":"Computational & experimental evaluation of the structure\/activity relationship of \u03b2-carbolines as DYRK1A inhibitors","volume":"24","author":"Drung","year":"2014","journal-title":"Bioorgan. Med. Chem. Lett."},{"key":"ref_211","doi-asserted-by":"crossref","unstructured":"R\u00fcben, K., Wurzlbauer, A., Walte, A., Sippl, W., Bracher, F., and Becker, W. (2015). Selectivity Profiling and Biological Activity of Novel \u03b2-Carbolines as Potent and Selective DYRK1 Kinase Inhibitors. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0132453"},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1016\/0014-4886(87)90231-7","article-title":"Harmala alkaloids and related beta-carbolines: A myoclonic model and antimyoclonic drugs","volume":"96","author":"Pranzatelli","year":"1987","journal-title":"Exp. Neurol."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1038\/nn1443","article-title":"Alpha-synuclein phosphorylation controls neurotoxicity and inclusion formation in a Drosophila model of Parkinson disease","volume":"8","author":"Chen","year":"2005","journal-title":"Nat. Neurosci."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1042\/bj20021535","article-title":"The specificities of protein kinase inhibitors: An update","volume":"371","author":"Bain","year":"2003","journal-title":"Biochem. J."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.physbeh.2017.05.003","article-title":"Epigallocatechin-3-gallate (EGCG) consumption in the Ts65Dn model of Down syndrome fails to improve behavioral deficits and is detrimental to skeletal phenotypes","volume":"177","author":"Stringer","year":"2017","journal-title":"Physiol. Behav."},{"key":"ref_216","doi-asserted-by":"crossref","unstructured":"Gu, Y., Moroy, G., Paul, J.-L., Rebillat, A.-S., Dierssen, M., de la Torre, R., Cieuta-Walti, C., Dairou, J., and Janel, N. (2020). Molecular Rescue of Dyrk1A Overexpression Alterations in Mice with Fontup (R) Dietary Supplement: Role of Green Tea Catechins. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21041404"},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"10426","DOI":"10.1038\/s41598-020-67133-z","article-title":"Evaluation of the therapeutic potential of Epigallocatechin-3-gallate (EGCG) via oral gavage in young adult Down syndrome mice","volume":"10","author":"Goodlett","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"4172","DOI":"10.1021\/jm200274d","article-title":"Leucettines, a class of potent inhibitors of cdc2-like kinases and dual specificity, tyrosine phosphorylation regulated kinases derived from the marine sponge leucettamine B: Modulation of alternative pre-RNA splicing","volume":"54","author":"Debdab","year":"2011","journal-title":"J. Med. Chem."},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1093\/hmg\/ddm086","article-title":"Duplication of the entire 22.9 Mb human chromosome 21 syntenic region on mouse chromosome 16 causes cardiovascular and gastrointestinal abnormalities","volume":"16","author":"Li","year":"2007","journal-title":"Hum. Mol. Genet."},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"2170","DOI":"10.1016\/j.euroneuro.2015.03.018","article-title":"Leucettine L41, a DYRK1A-preferential DYRKs\/CLKs inhibitor, prevents memory impairments and neurotoxicity induced by oligomeric A\u03b225-35 peptide administration in mice","volume":"25","author":"Naert","year":"2015","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"9569","DOI":"10.1021\/jm401049v","article-title":"Development of DANDYs, new 3,5-diaryl-7-azaindoles demonstrating potent DYRK1A kinase inhibitory activity","volume":"56","author":"Gourdain","year":"2013","journal-title":"J. Med. Chem."},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"4434","DOI":"10.1016\/j.bmc.2015.06.018","article-title":"Design and synthesis of a potent inhibitor of class 1 DYRK kinases as a suppressor of adipogenesis","volume":"23","author":"Masaki","year":"2015","journal-title":"Bioorgan. Med. Chem."},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"12728","DOI":"10.1038\/srep12728","article-title":"Identification of a DYRK1A Inhibitor that Induces Degradation of the Target Kinase using Co-chaperone CDC37 fused with Luciferase nanoKAZ","volume":"5","author":"Sonamoto","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"1669","DOI":"10.1021\/ja309304m","article-title":"Small-molecule inducer of \u03b2 cell proliferation identified by high-throughput screening","volume":"135","author":"Shen","year":"2013","journal-title":"J. Am. Chem. Soc."},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"8372","DOI":"10.1038\/ncomms9372","article-title":"Inhibition of DYRK1A and GSK3B induces human \u03b2-cell proliferation","volume":"6","author":"Shen","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"10268","DOI":"10.1073\/pnas.1704143114","article-title":"Prenatal neurogenesis induction therapy normalizes brain structure and function in Down syndrome mice","volume":"114","author":"Awaya","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"3914","DOI":"10.1038\/s41598-019-40328-9","article-title":"Prenatal treatment with EGCG enriched green tea extract rescues GAD67 related developmental and cognitive defects in Down syndrome mouse models","volume":"9","author":"Souchet","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.freeradbiomed.2017.10.002","article-title":"GABAergic over-inhibition, a promising hypothesis for cognitive deficits in Down syndrome","volume":"114","author":"Delabar","year":"2018","journal-title":"Free Radic. Biol. Med."},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"54","DOI":"10.3389\/fncel.2017.00054","article-title":"The GABAergic Hypothesis for Cognitive Disabilities in Down Syndrome","volume":"11","author":"Contestabile","year":"2017","journal-title":"Front. Cell Neurosci."},{"key":"ref_230","first-page":"4856","article-title":"Influence of prenatal EGCG treatment and Dyrk1a dosage reduction on craniofacial features associated with Down syndrome","volume":"25","author":"McElyea","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.neuroscience.2016.07.031","article-title":"Short- and long-term effects of neonatal pharmacotherapy with epigallocatechin-3-gallate on hippocampal development in the Ts65Dn mouse model of Down syndrome","volume":"333","author":"Stagni","year":"2016","journal-title":"Neuroscience"},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"4715","DOI":"10.1038\/s41598-021-83757-1","article-title":"Green tea extracts containing epigallocatechin-3-gallate modulate facial development in Down syndrome","volume":"11","author":"Starbuck","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1016\/j.clnu.2019.05.028","article-title":"Effect of epigallocatechin gallate on the body composition and lipid profile of down syndrome individuals: Implications for clinical management","volume":"39","author":"Xicota","year":"2020","journal-title":"Clin. Nutr."},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"6540","DOI":"10.1093\/hmg\/ddv364","article-title":"Genetic dissection of the Down syndrome critical region","volume":"24","author":"Jiang","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"ref_235","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1093\/hmg\/ddy447","article-title":"Cbs overdosage is necessary and sufficient to induce cognitive phenotypes in mouse models of Down syndrome and interacts genetically with Dyrk1a","volume":"28","author":"Marechal","year":"2019","journal-title":"Hum. Mol. 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