Generic placeholder image

Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

DYRK1A Inhibitors and Perspectives for the Treatment of Alzheimer's Disease

Author(s): Márcia Maria de Souza, Arthur Ribeiro Cenci, Kerolain Faoro Teixeira, Valkiria Machado, Majory Christina Garcia Mendes Schuler, Ana Elisa Gonçalves, Ana Paula Dalmagro, Camila André Cazarin, Leonardo Luiz Gomes Ferreira, Aldo Sena de Oliveira and Adriano Defini Andricopulo*

Volume 30, Issue 6, 2023

Published on: 29 August, 2022

Page: [669 - 688] Pages: 20

DOI: 10.2174/0929867329666220620162018

Price: $65

Abstract

Background: Alzheimer's disease (AD) is a chronic neurodegenerative disease and the most common form of dementia, especially in the elderly. Due to the increase in life expectancy, in recent years, there has been an excessive growth in the number of people affected by this disease, causing serious problems for health systems. In recent years, research has been intensified to find new therapeutic approaches that prevent the progression of the disease. In this sense, recent studies indicate that the dual-specificity tyrosine phosphorylation regulated kinase 1A (DYRK1A) gene, which is located on chromosome 21q22.2 and overexpressed in Down syndrome (DS), may play a significant role in developmental brain disorders and early onset neurodegeneration, neuronal loss and dementia in DS and AD. Inhibiting DYRK1A may serve to stop the phenotypic effects of its overexpression and, therefore, is a potential treatment strategy for the prevention of ageassociated neurodegeneration, including Alzheimer-type pathology.

Objective: In this review, we investigate the contribution of DYRK1A inhibitors as potential anti-AD agents.

Methods: A search in the literature to compile an in vitro dataset including IC50 values involving DYRK1A was performed from 2014 to the present day. In addition, we carried out structure-activity relationship studies based on in vitro and in silico data.

Results: molecular modeling and enzyme kinetics studies indicate that DYRK1A may contribute to AD pathology through its proteolytic process, reducing its kinase specificity.

Conclusion: further evaluation of DYRK1A inhibitors may contribute to new therapeutic approaches for AD.

Keywords: Alzheimer’s disease, neurodegeneration, protein kinases, enzyme kinetics, DYRK1A inhibitors, molecular docking.

[1]
Ahuja, L.G.; Taylor, S.S.; Kornev, A.P. Tuning the “violin” of protein kinases: The role of dynamics-based allostery. IUBMB Life, 2019, 71(6), 685-696.
[http://dx.doi.org/10.1002/iub.2057] [PMID: 31063633]
[2]
Govoni, S.; Amadio, M.; Battaini, F.; Pascale, A. Senescence of the brain: Focus on cognitive kinases. Curr. Pharm. Des., 2010, 16(6), 660-671.
[http://dx.doi.org/10.2174/138161210790883732] [PMID: 20388076]
[3]
Borodinova, A.A.; Zuzina, A.B.; Balaban, P.M. Role of atypical protein kinases in maintenance of long-term memory and synaptic plasticity. Biochemistry (Mosc.), 2017, 82(3), 243-256.
[http://dx.doi.org/10.1134/S0006297917030026] [PMID: 28320265]
[4]
van der Zee, E.A. Synapses, spines and kinases in mammalian learning and memory, and the impact of aging. Neurosci. Biobehav. Rev., 2015, 50, 77-85.
[http://dx.doi.org/10.1016/j.neubiorev.2014.06.012] [PMID: 24998408]
[5]
Kim, N.; Chen, D.; Zhou, X.Z.; Lee, T.H. Death-associated protein kinase 1 phosphorylation in neuronal cell death and neurodegenerative disease. Int. J. Mol. Sci., 2019, 20, 3131.
[6]
Nygaard, H.B. Targeting Fyn Kinase in Alzheimer’s Disease. Biol. Psychiatry, 2018, 83(4), 369-376.
[http://dx.doi.org/10.1016/j.biopsych.2017.06.004] [PMID: 28709498]
[7]
Pickrell, A.M.; Youle, R.J. The roles of PINK1, parkin, and mitochondrial fidelity in Parkinson’s disease. Neuron, 2015, 85(2), 257-273.
[http://dx.doi.org/10.1016/j.neuron.2014.12.007] [PMID: 25611507]
[8]
Arbones, M.L.; Thomazeau, A.; Nakano-Kobayashi, A.; Hagiwara, M.; Delabar, J.M. DYRK1A and cognition: A lifelong relationship. Pharmacol. Ther., 2019, 194, 199-221.
[http://dx.doi.org/10.1016/j.pharmthera.2018.09.010] [PMID: 30268771]
[9]
Feki, A.; Hibaoui, Y. DYRK1A protein, a promising therapeutic target to improve cognitive deficits in down syndrome. Brain Sci., 2018, 8(10), 8.
[http://dx.doi.org/10.3390/brainsci8100187] [PMID: 30332747]
[10]
Becker, W.; Joost, H.G. Structural and functional characteristics of Dyrk, a novel subfamily of protein kinases with dual specificity. Prog. Nucleic Acid Res. Mol. Biol., 1999, 62, 1-17.
[PMID: 9932450]
[11]
Arranz, J.; Balducci, E.; Arató, K.; Sánchez-Elexpuru, G.; Najas, S.; Parras, A.; Rebollo, E.; Pijuan, I.; Erb, I.; Verde, G.; Sahun, I.; Barallobre, M.J.; Lucas, J.J.; Sánchez, M.P.; de la Luna, S.; Arbonés, M.L. Impaired development of neocortical circuits contributes to the neurological alterations in DYRK1A haploinsufficiency syndrome. Neurobiol. Dis., 2019, 127, 210-222.
[http://dx.doi.org/10.1016/j.nbd.2019.02.022] [PMID: 30831192]
[12]
Shaikh, M.N.; Tejedor, F.J. Mnb/Dyrk1A orchestrates a transcriptional network at the transition from self-renewing neurogenic progenitors to postmitotic neuronal precursors. J. Neurogenet., 2018, 32(1), 37-50.
[http://dx.doi.org/10.1080/01677063.2018.1438427] [PMID: 29495936]
[13]
Yin, X.; Jin, N.; Shi, J.; Zhang, Y.; Wu, Y.; Gong, C.X.; Iqbal, K.; Liu, F. Dyrk1A overexpression leads to increase of 3R-tau expression and cognitive deficits in Ts65Dn Down syndrome mice. Sci. Rep., 2017, 7(1), 619.
[http://dx.doi.org/10.1038/s41598-017-00682-y] [PMID: 28377597]
[14]
Fructuoso, M.; Gu, Y.C.; Kassis, N.; de Lagran, M.M.; Dierssen, M.; Janel, N. Ethanol-induced changes in brain of transgenic mice overexpressing DYRK1A. Mol. Neurobiol., 2020, 57(7), 3195-3205.
[http://dx.doi.org/10.1007/s12035-020-01967-6] [PMID: 32504418]
[15]
Li, W.; Pozzo-Miller, L. Dysfunction of the corticostriatal pathway in autism spectrum disorders. J. Neurosci. Res., 2020, 98(11), 2130-2147.
[http://dx.doi.org/10.1002/jnr.24560] [PMID: 31758607]
[16]
Quiñones-Lombraña, A.; Blanco, J.G. Comparative analysis of the DYRK1A-SRSF6-TNNT2 pathway in myocardial tissue from individuals with and without Down syndrome. Exp. Mol. Pathol., 2019, 110, 104268.
[http://dx.doi.org/10.1016/j.yexmp.2019.104268] [PMID: 31201803]
[17]
Kargbo, R.B. Selective DYRK1A inhibitor for the treatment of neurodegenerative diseases: Alzheimer, Parkinson, Huntington, and Down Syndrome. ACS Med. Chem. Lett., 2020, 11(10), 1795-1796.
[http://dx.doi.org/10.1021/acsmedchemlett.0c00346] [PMID: 33062155]
[18]
Lane, C.A.; Hardy, J.; Schott, J.M. Alzheimer’s disease. Eur. J. Neurol., 2018, 25(1), 59-70.
[http://dx.doi.org/10.1111/ene.13439] [PMID: 28872215]
[19]
Hodson, R. Alzheimer’s disease. Nature, 2018, 559(7715), S1.
[http://dx.doi.org/10.1038/d41586-018-05717-6] [PMID: 30046078]
[20]
An, Y.; Varma, V.R.; Varma, S.; Casanova, R.; Dammer, E.; Pletnikova, O.; Chia, C.W.; Egan, J.M.; Ferrucci, L.; Troncoso, J.; Levey, A.I.; Lah, J.; Seyfried, N.T.; Legido-Quigley, C.; O’Brien, R.; Thambisetty, M. Evidence for brain glucose dysregulation in Alzheimer’s disease. Alzheimers Dement., 2018, 14(3), 318-329.
[http://dx.doi.org/10.1016/j.jalz.2017.09.011] [PMID: 29055815]
[21]
McDade, E.; Bateman, R.J. Stop Alzheimer’s before it starts. Nature, 2017, 547(7662), 153-155.
[http://dx.doi.org/10.1038/547153a] [PMID: 28703214]
[22]
Tiwari, S.; Atluri, V.; Kaushik, A.; Yndart, A.; Nair, M. Alzheimer’s disease: Pathogenesis, diagnostics, and therapeutics. Int. J. Nanomedicine, 2019, 14, 5541-5554.
[http://dx.doi.org/10.2147/IJN.S200490] [PMID: 31410002]
[23]
Gallardo, G.; Holtzman, D.M. Amyloid-β and tau at the crossroads of Alzheimer’s disease. In: Advances in Experimental Medicine and Biology; Springer, 2019; Vol. 1184, pp. 187-203.
[24]
Martinez, A.; Castro, A. Novel cholinesterase inhibitors as future effective drugs for the treatment of Alzheimer’s disease. Expert Opin. Investig. Drugs, 2006, 15(1), 1-12.
[http://dx.doi.org/10.1517/13543784.15.1.1] [PMID: 16370929]
[25]
Ferreira-Vieira, T.H.; Guimaraes, I.M.; Silva, F.R.; Ribeiro, F.M. Alzheimer’s disease: Targeting the cholinergic system. Curr. Neuropharmacol., 2016, 14(1), 101-115.
[http://dx.doi.org/10.2174/1570159X13666150716165726] [PMID: 26813123]
[26]
Chen, X.Q.; Mobley, W.C. Exploring the pathogenesis of Alzheimer disease in basal forebrain cholinergic neurons: Converging insights from alternative hypotheses. Front. Neurosci., 2019, 13, 446.
[http://dx.doi.org/10.3389/fnins.2019.00446] [PMID: 31133787]
[27]
Stanciu, G.D.; Luca, A.; Rusu, R.N.; Bild, V.; Beschea Chiriac, S.I.; Solcan, C.; Bild, W.; Ababei, D.C. Alzheimer’s disease pharmacotherapy in relation to cholinergic system involvement. Biomolecules, 2019, 10(1), 40.
[http://dx.doi.org/10.3390/biom10010040] [PMID: 31888102]
[28]
Jouanne, M.; Rault, S.; Voisin-Chiret, A.S. Tau protein aggregation in Alzheimer’s disease: An attractive target for the development of novel therapeutic agents. Eur. J. Med. Chem., 2017, 139, 153-167.
[http://dx.doi.org/10.1016/j.ejmech.2017.07.070] [PMID: 28800454]
[29]
Ferrer, I.; Barrachina, M.; Puig, B.; Martínez de Lagrán, M.; Martí, E.; Avila, J.; Dierssen, M. Constitutive Dyrk1A is abnormally expressed in Alzheimer disease, Down syndrome, Pick disease, and related transgenic models. Neurobiol. Dis., 2005, 20(2), 392-400.
[http://dx.doi.org/10.1016/j.nbd.2005.03.020] [PMID: 16242644]
[30]
Kozlov, S.; Afonin, A.; Evsyukov, I.; Bondarenko, A. Alzheimer’s disease: As it was in the beginning. Rev. Neurosci., 2017, 28(8), 825-843.
[http://dx.doi.org/10.1515/revneuro-2017-0006] [PMID: 28704198]
[31]
Hampel, H.; Caraci, F.; Cuello, A.C.; Caruso, G.; Nisticò, R.; Corbo, M.; Baldacci, F.; Toschi, N.; Garaci, F.; Chiesa, P.A.; Verdooner, S.R.; Akman-Anderson, L.; Hernández, F.; Ávila, J.; Emanuele, E.; Valenzuela, P.L.; Lucía, A.; Watling, M.; Imbimbo, B.P.; Vergallo, A.; Lista, S. A path toward precision medicine for neuroinflammatory mechanisms in Alzheimer’s disease. Front. Immunol., 2020, 11, 456.
[http://dx.doi.org/10.3389/fimmu.2020.00456] [PMID: 32296418]
[32]
Colonna, M.; Brioschi, S. Neuroinflammation and neurodegeneration in human brain at single-cell resolution. Nat. Rev. Immunol., 2020, 20(2), 81-82.
[http://dx.doi.org/10.1038/s41577-019-0262-0] [PMID: 31844328]
[33]
Webers, A.; Heneka, M.T.; Gleeson, P.A. The role of innate immune responses and neuroinflammation in amyloid accumulation and progression of Alzheimer’s disease. Immunol. Cell Biol., 2020, 98(1), 28-41.
[http://dx.doi.org/10.1111/imcb.12301] [PMID: 31654430]
[34]
Minter, M.R.; Taylor, J.M.; Crack, P.J. The contribution of neuroinflammation to amyloid toxicity in Alzheimer’s disease. J. Neurochem., 2016, 136(3), 457-474.
[http://dx.doi.org/10.1111/jnc.13411] [PMID: 26509334]
[35]
Castellano, J.M.; Kim, J.; Stewart, F.R.; Jiang, H.; DeMattos, R.B.; Patterson, B.W.; Fagan, A.M.; Morris, J.C.; Mawuenyega, K.G.; Cruchaga, C.; Goate, A.M.; Bales, K.R.; Paul, S.M.; Bateman, R.J.; Holtzman, D.M. Human apoE isoforms differentially regulate brain amyloid-β peptide clearance. Sci. Transl. Med., 2011, 3(89), 89ra57.
[http://dx.doi.org/10.1126/scitranslmed.3002156] [PMID: 21715678]
[36]
Verghese, P.B.; Castellano, J.M.; Garai, K.; Wang, Y.; Jiang, H.; Shah, A.; Bu, G.; Frieden, C.; Holtzman, D.M.; Apo, E. ApoE influences amyloid-β (Aβ) clearance despite minimal apoE/Aβ association in physiological conditions. Proc. Natl. Acad. Sci. USA, 2013, 110(19), E1807-E1816.
[http://dx.doi.org/10.1073/pnas.1220484110] [PMID: 23620513]
[37]
Goate, A.; Chartier-Harlin, M.C.; Mullan, M.; Brown, J.; Crawford, F.; Fidani, L.; Giuffra, L.; Haynes, A.; Irving, N.; James, L.; Mant, R.; Newton, P.; Rooke, K.; Roques, P.; Talbot, C.; Pericak-Vance, M.; Roses, A.; Williamson, R.; Rossor, M.; Owen, M.; Hardy, J. Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer’s disease. Nature, 1991, 349(6311), 704-706.
[http://dx.doi.org/10.1038/349704a0] [PMID: 1671712]
[38]
Sherrington, R.; Rogaev, E.I.; Liang, Y.; Rogaeva, E.A.; Levesque, G.; Ikeda, M.; Chi, H.; Lin, C.; Li, G.; Holman, K.; Tsuda, T.; Mar, L.; Foncin, J.F.; Bruni, A.C.; Montesi, M.P.; Sorbi, S.; Rainero, I.; Pinessi, L.; Nee, L.; Chumakov, I.; Pollen, D.; Brookes, A.; Sanseau, P.; Polinsky, R.J.; Wasco, W.; Da Silva, H.A.R.; Haines, J.L.; Perkicak-Vance, M.A.; Tanzi, R.E.; Roses, A.D.; Fraser, P.E.; Rommens, J.M.; St George-Hyslop, P.H. Cloning of a gene bearing missense mutations in early-onset familial Alzheimer’s disease. Nature, 1995, 375(6534), 754-760.
[http://dx.doi.org/10.1038/375754a0] [PMID: 7596406]
[39]
Levy-Lahad, E.; Wijsman, E.M.; Nemens, E.; Anderson, L.; Goddard, K.A.B.; Weber, J.L.; Bird, T.D.; Schellenberg, G.D. A familial Alzheimer’s disease locus on chromosome. iScience, 1995, 269, 970-973.
[40]
Rogaev, E.I.; Sherrington, R.; Rogaeva, E.A.; Levesque, G.; Ikeda, M.; Liang, Y.; Chi, H.; Lin, C.; Holman, K.; Tsuda, T.; Mar, L.; Sorbi, S.; Nacmias, B.; Piacentini, S.; Amaducci, L.; Chumakov, I.; Cohen, D.; Lannfelt, L.; Fraser, P.E.; Rommens, J.M.; George-Hyslop, P.H.S. Familial Alzheimer’s disease in kindreds with missense mutations in a gene on chromosome 1 related to the Alzheimer’s disease type 3 gene. Nature, 1995, 376(6543), 775-778.
[http://dx.doi.org/10.1038/376775a0] [PMID: 7651536]
[41]
Karch, C.M.; Goate, A.M. Alzheimer’s disease risk genes and mechanisms of disease pathogenesis. Biol. Psychiatry, 2015, 77(1), 43-51.
[http://dx.doi.org/10.1016/j.biopsych.2014.05.006] [PMID: 24951455]
[42]
de Nazareth, A.M. Type 2 diabetes mellitus in the pathophysiology of Alzheimer’s disease. Dement. Neuropsychol., 2017, 11(2), 105-113.
[http://dx.doi.org/10.1590/1980-57642016dn11-020002] [PMID: 29213501]
[43]
Hsu, H.W.; Bondy, S.C.; Kitazawa, M. Environmental and dietary exposure to copper and its cellular mechanisms linking to Alzheimer’s disease. Toxicol. Sci., 2018, 163(2), 338-345.
[http://dx.doi.org/10.1093/toxsci/kfy025] [PMID: 29409005]
[44]
Banerjee, A.; Khemka, V.K.; Roy, D.; Dhar, A.; Sinha Roy, T.K.; Biswas, A.; Mukhopadhyay, B.; Chakrabarti, S. Role of pro-inflammatory cytokines and vitamin D in probable Alzheimer’s disease with depression. Aging Dis., 2017, 8(3), 267-276.
[http://dx.doi.org/10.14336/AD.2016.1017] [PMID: 28580183]
[45]
A., Armstrong R. Risk factors for Alzheimer’s disease. Folia Neuropathol., 2019, 57(2), 87-105.
[http://dx.doi.org/10.5114/fn.2019.85929] [PMID: 31556570]
[46]
Silva, M.V.F.; Loures, C.M.G.; Alves, L.C.V.; de Souza, L.C.; Borges, K.B.G.; Carvalho, M.D.G. Alzheimer’s disease: Risk factors and potentially protective measures. J. Biomed. Sci., 2019, 26(1), 33.
[http://dx.doi.org/10.1186/s12929-019-0524-y] [PMID: 31072403]
[47]
Tejedor, F.; Zhu, X.R.; Kaltenbach, E.; Ackermann, A.; Baumann, A.; Canal, I.; Heisenberg, M.; Fischbach, K.F.; Pongs, O. minibrain: A new protein kinase family involved in postembryonic neurogenesis in Drosophila. Neuron, 1995, 14(2), 287-301.
[http://dx.doi.org/10.1016/0896-6273(95)90286-4] [PMID: 7857639]
[48]
Mozzi, A.; Forni, D.; Cagliani, R.; Pozzoli, U.; Clerici, M.; Sironi, M. Distinct selective forces and Neanderthal introgression shaped genetic diversity at genes involved in neurodevelopmental disorders. Sci. Rep., 2017, 7(1), 6116.
[http://dx.doi.org/10.1038/s41598-017-06440-4] [PMID: 28733602]
[49]
Song, W.J.; Sternberg, L.R.; Kasten-Sportès, C.; Keuren, M.L.; Chung, S.H.; Slack, A.C.; Miller, D.E.; Glover, T.W.; Chiang, P.W.; Lou, L.; Kurnit, D.M. Isolation of human and murine homologues of the Drosophila minibrain gene: Human homologue maps to 21q22.2 in the Down syndrome “critical region”. Genomics, 1996, 38(3), 331-339.
[http://dx.doi.org/10.1006/geno.1996.0636] [PMID: 8975710]
[50]
Martínez-Cué, C.; Rueda, N. Signalling pathways implicated in Alzheimer’s disease neurodegeneration in individuals with and without Down Syndrome. Int. J. Mol. Sci., 2020, 21(18), 1-36.
[http://dx.doi.org/10.3390/ijms21186906] [PMID: 32962300]
[51]
Hämmerle, B.; Ulin, E.; Guimera, J.; Becker, W.; Guillemot, F.; Tejedor, F.J. Transient expression of Mnb/Dyrk1a couples cell cycle exit and differentiation of neuronal precursors by inducing p27KIP1 expression and suppressing NOTCH signaling. Development, 2011, 138(12), 2543-2554.
[http://dx.doi.org/10.1242/dev.066167] [PMID: 21610031]
[52]
Hämmerle, B.; Carnicero, A.; Elizalde, C.; Ceron, J.; Martínez, S.; Tejedor, F.J. Expression patterns and subcellular localization of the Down syndrome candidate protein MNB/DYRK1A suggest a role in late neuronal differentiation. Eur. J. Neurosci., 2003, 17(11), 2277-2286.
[http://dx.doi.org/10.1046/j.1460-9568.2003.02665.x] [PMID: 12814361]
[53]
Tejedor, F.J.; Hämmerle, B. MNB/DYRK1A as a multiple regulator of neuronal development. FEBS J., 2011, 278(2), 223-235.
[http://dx.doi.org/10.1111/j.1742-4658.2010.07954.x] [PMID: 21156027]
[54]
Park, J.; Song, W.J.; Chung, K.C. Function and regulation of Dyrk1A: Towards understanding Down syndrome. Cell. Mol. Life Sci., 2009, 66(20), 3235-3240.
[http://dx.doi.org/10.1007/s00018-009-0123-2] [PMID: 19685005]
[55]
Lee, Y.H. Im, E.; Hyun, M.; Park, J.; Chung, K.C. Protein phosphatase PPM1B inhibits DYRK1A kinase through dephosphorylation of pS258 and reduces toxic tau aggregation. J. Biol. Chem., 2021, 296, 100245.
[http://dx.doi.org/10.1074/jbc.RA120.015574] [PMID: 33380426]
[56]
Fortea, J.; Vilaplana, E.; Carmona-Iragui, M.; Benejam, B.; Videla, L.; Barroeta, I.; Fernández, S.; Altuna, M.; Pegueroles, J.; Montal, V.; Valldeneu, S.; Giménez, S.; González-Ortiz, S.; Muñoz, L.; Estellés, T.; Illán-Gala, I.; Belbin, O.; Camacho, V.; Wilson, L.R.; Annus, T.; Osorio, R.S.; Videla, S.; Lehmann, S.; Holland, A.J.; Alcolea, D.; Clarimón, J.; Zaman, S.H.; Blesa, R.; Lleó, A. Clinical and biomarker changes of Alzheimer’s disease in adults with Down syndrome: A cross-sectional study. Lancet, 2020, 395(10242), 1988-1997.
[http://dx.doi.org/10.1016/S0140-6736(20)30689-9] [PMID: 32593336]
[57]
Carmona-Iragui, M.; Videla, L.; Lleó, A.; Fortea, J. Down syndrome, Alzheimer disease, and cerebral amyloid angiopathy: The complex triangle of brain amyloidosis. Dev. Neurobiol., 2019, 79(7), 716-737.
[http://dx.doi.org/10.1002/dneu.22709] [PMID: 31278851]
[58]
Liu, F.; Liang, Z.; Wegiel, J.; Hwang, Y.W.; Iqbal, K.; Grundke-Iqbal, I.; Ramakrishna, N.; Gong, C.X. Overexpression of Dyrk1A contributes to neurofibrillary degeneration in Down syndrome. FASEB J., 2008, 22(9), 3224-3233.
[http://dx.doi.org/10.1096/fj.07-104539] [PMID: 18509201]
[59]
Ryoo, S.R.; Jeong, H.K.; Radnaabazar, C.; Yoo, J.J.; Cho, H.J.; Lee, H.W.; Kim, I.S.; Cheon, Y.H.; Ahn, Y.S.; Chung, S.H.; Song, W.J. DYRK1A-mediated hyperphosphorylation of Tau. A functional link between Down syndrome and Alzheimer disease. J. Biol. Chem., 2007, 282(48), 34850-34857.
[http://dx.doi.org/10.1074/jbc.M707358200] [PMID: 17906291]
[60]
Coutadeur, S.; Benyamine, H.; Delalonde, L.; de Oliveira, C.; Leblond, B.; Foucourt, A.; Besson, T.; Casagrande, A.S.; Taverne, T.; Girard, A.; Pando, M.P.; Désiré, L. A novel DYRK1A (dual specificity tyrosine phosphorylation-regulated kinase 1A) inhibitor for the treatment of Alzheimer’s disease: Effect on Tau and amyloid pathologies in vitro. J. Neurochem., 2015, 133(3), 440-451.
[http://dx.doi.org/10.1111/jnc.13018] [PMID: 25556849]
[61]
Janel, N.; Sarazin, M.; Corlier, F.; Corne, H.; de Souza, L.C.; Hamelin, L.; Aka, A.; Lagarde, J.; Blehaut, H.; Hindié, V.; Rain, J.C.; Arbones, M.L.; Dubois, B.; Potier, M.C.; Bottlaender, M.; Delabar, J.M. Plasma DYRK1A as a novel risk factor for Alzheimer’s disease. Transl. Psychiatry, 2014, 4(8), e425.
[http://dx.doi.org/10.1038/tp.2014.61] [PMID: 25116835]
[62]
Delabar, J.M.; Ortner, M.; Simon, S.; Wijkhuisen, A.; Feraudet-Tarisse, C.; Pegon, J.; Vidal, E.; Hirschberg, Y.; Dubois, B.; Potier, M.C. Altered age-linked regulation of plasma DYRK1A in elderly cognitive complainers (INSIGHT-PreAD Study) with high brain amyloid load. Alzheimer’s Dement. Transl. Res. Clin. Interv, 2020, 2020, 6.
[63]
Murphy, M.P.; LeVine, H., III Alzheimer’s disease and the amyloid-β peptide. J. Alzheimers Dis., 2010, 19(1), 311-323.
[http://dx.doi.org/10.3233/JAD-2010-1221] [PMID: 20061647]
[64]
Paasila, P.J.; Davies, D.S.; Kril, J.J.; Goldsbury, C.; Sutherland, G.T. The relationship between the morphological subtypes of microglia and Alzheimer’s disease neuropathology. Brain Pathol., 2019, 29(6), 726-740.
[http://dx.doi.org/10.1111/bpa.12717] [PMID: 30803086]
[65]
Madav, Y.; Wairkar, S.; Prabhakar, B. Recent therapeutic strategies targeting beta amyloid and tauopathies in Alzheimer’s disease. Brain Res. Bull., 2019, 146, 171-184.
[http://dx.doi.org/10.1016/j.brainresbull.2019.01.004] [PMID: 30634016]
[66]
Lee, H.J.; Woo, H.; Lee, H.E.; Jeon, H.; Ryu, K.Y.; Nam, J.H.; Jeon, S.G.; Park, H.; Lee, J.S.; Han, K.M.; Lee, S.M.; Kim, J.; Kang, R.J.; Lee, Y.H.; Kim, J.I.; Hoe, H.S. The novel DYRK1A inhibitor KVN93 regulates cognitive function, amyloid-beta pathology, and neuroinflammation. Free Radic. Biol. Med., 2020, 160, 575-595.
[http://dx.doi.org/10.1016/j.freeradbiomed.2020.08.030] [PMID: 32896600]
[67]
Martin, L.; Latypova, X.; Wilson, C.M.; Magnaudeix, A.; Perrin, M.L.; Yardin, C.; Terro, F. Tau protein kinases: Involvement in Alzheimer’s disease. Ageing Res. Rev., 2013, 12(1), 289-309.
[http://dx.doi.org/10.1016/j.arr.2012.06.003] [PMID: 22742992]
[68]
Wegiel, J.; Gong, C.X.; Hwang, Y.W. The role of DYRK1A in neurodegenerative diseases. FEBS J., 2011, 278(2), 236-245.
[http://dx.doi.org/10.1111/j.1742-4658.2010.07955.x] [PMID: 21156028]
[69]
Kay, L.J.; Smulders-Srinivasan, T.K.; Soundararajan, M. Understanding the multifaceted role of human Down Syndrome kinase DYRK1A. Adv. Protein Chem. Struct. Biol., 2016, 105, 127-171.
[http://dx.doi.org/10.1016/bs.apcsb.2016.07.001] [PMID: 27567487]
[70]
Lagunes, T.; Herrera-Rivero, M.; Hernández-Aguilar, M.E.; Aranda-Abreu, G. Abeta(1-42) Induces abnormal alternative splicing of tau exons 2/3 in NGF-Induced PC12 cells. An. Acad. Bras. Cienc., 2014, 86(4), 1927-1934.
[http://dx.doi.org/10.1590/0001-3765201420130333]
[71]
Pathak, A.; Rohilla, A.; Gupta, T.; Akhtar, M.J.; Haider, M.R.; Sharma, K.; Haider, K.; Yar, M.S. DYRK1A kinase inhibition with emphasis on neurodegeneration: A comprehensive evolution story-cum-perspective. Eur. J. Med. Chem., 2018, 158, 559-592.
[http://dx.doi.org/10.1016/j.ejmech.2018.08.093] [PMID: 30243157]
[72]
Azorsa, D.O.; Robeson, R.L.H.; Frost, D. hoovet, B.M.; Brautigam, G.R.; Dickey, C.; Beaudry, C.; Basu, G.D.; Holz, D.R.; Hernandez, J.A.; Bisanz, K.M.; Gwinn, L.; Grover, A.; Rogers, J.; Reiman, E.M.; Hutton, M.; Stephan, D.A.; Mousses, S.; Dunckley, T. High-Content SiRNA screening of the kinome identifies Kinases involved in Alzheimer’s Disease-related Tau Hyperphosphorylation. BMC Genomics, 2010, 2010, 11.
[73]
Branca, C.; Shaw, D.M.; Belfiore, R.; Gokhale, V.; Shaw, A.Y.; Foley, C.; Smith, B.; Hulme, C.; Dunckley, T.; Meechoovet, B.; Caccamo, A.; Oddo, S. Dyrk1 inhibition improves Alzheimer’s disease-like pathology. Aging Cell, 2017, 16(5), 1146-1154.
[http://dx.doi.org/10.1111/acel.12648] [PMID: 28779511]
[74]
García-Cerro, S.; Rueda, N.; Vidal, V.; Lantigua, S.; Martínez-Cué, C. Normalizing the gene dosage of Dyrk1A in a mouse model of Down syndrome rescues several Alzheimer’s disease phenotypes. Neurobiol. Dis., 2017, 106, 76-88.
[http://dx.doi.org/10.1016/j.nbd.2017.06.010] [PMID: 28647555]
[75]
Hampel, H.; Mesulam, M.M.; Cuello, A.C.; Farlow, M.R.; Giacobini, E.; Grossberg, G.T.; Khachaturian, A.S.; Vergallo, A.; Cavedo, E.; Snyder, P.J.; Khachaturian, Z.S. The cholinergic system in the pathophysiology and treatment of Alzheimer’s disease. Brain, 2018, 141(7), 1917-1933.
[http://dx.doi.org/10.1093/brain/awy132] [PMID: 29850777]
[76]
Breijyeh, Z.; Karaman, R. Comprehensive review on Alzheimer’s disease: Causes and treatment. Molecules, 2020, 25, 5789.
[77]
Hijazi, M.; Fillat, C.; Medina, J.M.; Velasco, A. Overexpression of DYRK1A inhibits choline acetyltransferase induction by oleic acid in cellular models of Down syndrome. Exp. Neurol., 2013, 239, 229-234.
[http://dx.doi.org/10.1016/j.expneurol.2012.10.016] [PMID: 23124096]
[78]
Regen, F.; Hellmann-Regen, J.; Costantini, E.; Reale, M. Neuroinflammation and Alzheimer’s disease: Implications for microglial activation. Curr. Alzheimer Res., 2017, 14(11), 1140-1148.
[http://dx.doi.org/10.2174/1567205014666170203141717] [PMID: 28164764]
[79]
Sánchez-Sarasúa, S.; Fernández-Pérez, I.; Espinosa-Fernández, V.; Sánchez-Pérez, A.M.; Ledesma, J.C. Can we treat neuroinflammation in Alzheimer’s disease? Int. J. Mol. Sci., 2020, 21, 8751.
[80]
Gelders, G.; Baekelandt, V.; Van der Perren, A. Linking neuroinflammation and neurodegeneration in Parkinson’s disease. J. Immunol. Res., 2018, 2018, 4784268.
[http://dx.doi.org/10.1155/2018/4784268]
[81]
Jeohn, G-H.; Kong, L-Y.; Wilson, B.; Hudson, P.; Hong, J-S. Synergistic neurotoxic effects of combined treatments with cytokines in murine primary mixed neuron/glia cultures. J. Neuroimmunol., 1998, 85(1), 1-10.
[http://dx.doi.org/10.1016/S0165-5728(97)00204-X] [PMID: 9626992]
[82]
Frost, D.; Meechoovet, B.; Wang, T.; Gately, S.; Giorgetti, M.; Shcherbakova, I.; Dunckley, T. β-carboline compounds, including harmine, inhibit DYRK1A and tau phosphorylation at multiple Alzheimer’s disease-related sites. PLoS One, 2011, 6(5), e19264.
[http://dx.doi.org/10.1371/journal.pone.0019264] [PMID: 21573099]
[83]
Domingues, C. da Cruz e Silva, O.A.B.; Henriques, A.G. Impact of Cytokines and Chemokines on Alzheimer’s Disease neuropathological hallmarks. Curr. Alzheimer Res., 2017, 14(8), 870-882.
[84]
Kaur, D.; Sharma, V.; Deshmukh, R. Activation of microglia and astrocytes: A roadway to neuroinflammation and Alzheimer’s disease. Inflammopharmacology, 2019, 27, 663-677.
[85]
Laurent, C.; Buée, L.; Blum, D. Tau and neuroinflammation: What impact for Alzheimer’s Disease and Tauopathies? Biomed. J., 2018, 41(1), 21-33.
[http://dx.doi.org/10.1016/j.bj.2018.01.003] [PMID: 29673549]
[86]
Michalicova, A.; Majerova, P.; Kovac, A. Tau protein and its role in blood-brain barrier dysfunction. Front. Mol. Neurosci., 2020, 13, 570045.
[http://dx.doi.org/10.3389/fnmol.2020.570045] [PMID: 33100967]
[87]
Chandra, A.; Valkimadi, P-E.; Pagano, G.; Cousins, O.; Dervenoulas, G.; Politis, M. Applications of amyloid, tau, and neuroinflammation PET imaging to Alzheimer’s disease and mild cognitive impairment. Hum. Brain Mapp., 2019, 40(18), 5424-5442.
[http://dx.doi.org/10.1002/hbm.24782] [PMID: 31520513]
[88]
Leyns, C.E.G.; Holtzman, D.M. Glial contributions to neurodegeneration in tauopathies. Mol. Neurodegener., 2017, 12, 1-16.
[89]
Melchior, B.; Mittapalli, G.K.; Lai, C.; Duong-Polk, K.; Stewart, J.; Güner, B.; Hofilena, B.; Tjitro, A.; Anderson, S.D.; Herman, D.S.; Dellamary, L.; Swearingen, C.J.; Sunil, K.C.; Yazici, Y. Tau pathology reduction with SM07883, a novel, potent, and selective oral DYRK1A inhibitor: A potential therapeutic for Alzheimer’s disease. Aging Cell, 2019, 18(5), e13000.
[http://dx.doi.org/10.1111/acel.13000] [PMID: 31267651]
[90]
Moldogazieva, N.T.; Mokhosoev, I.M. Oxidative stress and advanced lipoxidation and glycation end products (ALEs and AGEs) in aging and age-related diseases. Oxid. Med. Cell. Longev., 2019, 2019, 3085756.
[91]
Cheignon, C.; Tomas, M.; Bonnefont-Rousselot, D.; Faller, P.; Hureau, C.; Collin, F. Oxidative stress and the amyloid beta peptide in Alzheimer’s disease. Redox Biol., 2018, 14, 450-464.
[http://dx.doi.org/10.1016/j.redox.2017.10.014] [PMID: 29080524]
[92]
Alavi Naini, S.M.; Soussi-Yanicostas, N. Tau hyperphosphorylation and oxidative stress, a critical vicious circle in neurodegenerative tauopathies? Oxid. Med. Cell. Longev., 2015, 2015, 151979.
[http://dx.doi.org/10.1155/2015/151979]
[93]
Nguyen, T.L.; Fruit, C.; Hérault, Y.; Meijer, L.; Besson, T. Dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) inhibitors: A survey of recent patent literature. Expert Opin. Ther. Pat., 2017, 27(11), 1183-1199.
[http://dx.doi.org/10.1080/13543776.2017.1360285] [PMID: 28766366]
[94]
Sebastiani, G.; Almeida-Toledano, L.; Serra-Delgado, M.; Navarro-Tapia, E.; Sailer, S.; Valverde, O.; Garcia-Algar, O.; Andreu-Fernández, V. Therapeutic effects of catechins in less common neurological and neurodegenerative disorders. Nutr, 2021, 13, 2232.
[95]
Pons-Espinal, M.; Martinez de Lagran, M.; Dierssen, M. Environmental enrichment rescues DYRK1A activity and hippocampal adult neurogenesis in TgDyrk1A. Neurobiol. Dis., 2013, 60, 18-31.
[http://dx.doi.org/10.1016/j.nbd.2013.08.008] [PMID: 23969234]
[96]
Stotani, Silvia; Giordanetto, Fabrizio; Medda, Federico DYRK1A inhibition as potential treatment for Alzheimer’s disease. Future Med. Chem., 2016, 681-696.
[97]
Bálint, B.; Wéber, C.; Cruzalegui, F.; Burbridge, M.; Kotschy, A. Structure-based design and synthesis of harmine derivatives with different selectivity profiles in kinase versus monoamine oxidase inhibition. ChemMedChem, 2017, 12(12), 932-939.
[http://dx.doi.org/10.1002/cmdc.201600539] [PMID: 28264138]
[98]
Ogawa, Y.; Nonaka, Y.; Goto, T.; Ohnishi, E.; Hiramatsu, T.; Kii, I.; Yoshida, M.; Ikura, T.; Onogi, H.; Shibuya, H.; Hosoya, T.; Ito, N.; Hagiwara, M. Development of a novel selective inhibitor of the Down syndrome-related kinase Dyrk1A. Nat. Commun., 2010, 1(1), 86.
[http://dx.doi.org/10.1038/ncomms1090] [PMID: 20981014]
[99]
Centre, cambridge crystallographic data (org.). In: GOLD User Guide; 2019.
[100]
Liu, W.; Liu, X.; Tian, L.; Gao, Y.; Liu, W.; Chen, H.; Jiang, X.; Xu, Z.; Ding, H.; Zhao, Q. Design, synthesis and biological evaluation of harmine derivatives as potent GSK-3β/DYRK1A dual inhibitors for the treatment of Alzheimer’s disease. Eur. J. Med. Chem., 2021, 222, 113554.
[http://dx.doi.org/10.1016/j.ejmech.2021.113554] [PMID: 34098466]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy