Galantamine-induced Amyloid-β Clearance Mediated via Stimulation of Microglial Nicotinic Acetylcholine Receptors
Open accessAbstract
Reduction of brain amyloid-β (Aβ) has been proposed as a therapeutic target for Alzheimer disease (AD), and microglial Aβ phagocytosis is noted as an Aβ clearance system in brains. Galantamine is an acetylcholinesterase inhibitor approved for symptomatic treatment of AD. Galantamine also acts as an allosterically potentiating ligand (APL) for nicotinic acetylcholine receptors (nAChRs). APL-binding site is located close to but distinct from that for acetylcholine on nAChRs, and FK1 antibody specifically binds to the APL-binding site without interfering with the acetylcholine-binding site. We found that in human AD brain, microglia accumulated on Aβ deposits and expressed α7 nAChRs including the APL-binding site recognized with FK1 antibody. Treatment of rat microglia with galantamine significantly enhanced microglial Aβ phagocytosis, and acetylcholine competitive antagonists as well as FK1 antibody inhibited the enhancement. Thus, the galantamine-enhanced microglial Aβ phagocytosis required the combined actions of an acetylcholine competitive agonist and the APL for nAChRs. Indeed, depletion of choline, an acetylcholine-competitive α7 nAChR agonist, from the culture medium impeded the enhancement. Similarly, Ca(2+) depletion or inhibition of the calmodulin-dependent pathways for the actin reorganization abolished the enhancement. These results suggest that galantamine sensitizes microglial α7 nAChRs to choline and induces Ca(2+) influx into microglia. The Ca(2+)-induced intracellular signaling cascades may then stimulate Aβ phagocytosis through the actin reorganization. We further demonstrated that galantamine treatment facilitated Aβ clearance in brains of rodent AD models. In conclusion, we propose a further advantage of galantamine in clinical AD treatment and microglial nAChRs as a new therapeutic target.
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Galantamine activates microglia resulting in enhanced Aβ clearance.
“Galantamine activates microglia resulting in enhanced Aβ clearance [16].”
From Galantamine Slows Down Plaque Formation and Behavioral Decline in the 5XFAD Mouse Model of Alzheimer’s Disease (2014) · cites this paper as [16]
Galantamine enhances microglial Aβ clearance.
“galantamine has been shown to enhance microglial Aβ clearance [16].”
From Galantamine Slows Down Plaque Formation and Behavioral Decline in the 5XFAD Mouse Model of Alzheimer’s Disease (2014) · cites this paper as [16]
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The Amyloid Hypothesis of Alzheimer’s Disease: Progress and Problems on the Road to Therapeutics
Hardy, J., & Selkoe, D. J. (2002) · Science · doi:10.1126/science.1072994 · Cited by 13,864 · see citing works
Massagué, J. (1998) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.67.1.753 · Cited by 7,571 · see citing works
Rho GTPases and the Actin Cytoskeleton
Hall, A. (1998) · Science · doi:10.1126/science.279.5350.509 · Cited by 6,138 · see citing works
Walsh, D. M., Klyubin, I., Fadeeva, J. V., Cullen, W. K., Anwyl, R., Wolfe, M. S., Rowan, M. J., & Selkoe, D. J. (2002) · Nature · doi:10.1038/416535a · Cited by 4,291 · see citing works
Alzheimer's Disease and Senile Dementia: Loss of Neurons in the Basal Forebrain
Whitehouse, P., Price, D., Struble, R., Clark, A., Coyle, J., & DeLong, M. R. (1982) · Science · doi:10.1126/science.7058341 · Cited by 3,627 · see citing works
SELECTIVE LOSS OF CENTRAL CHOLINERGIC NEURONS IN ALZHEIMER'S DISEASE
DAVIES, P. (1976) · The Lancet · doi:10.1016/s0140-6736(76)91936-x · Cited by 3,565 · see citing works
Immunization with amyloid-β attenuates Alzheimer-disease-like pathology in the PDAPP mouse
Schenk, D., Barbour, R., Dunn, W., Gordon, G., Grajeda, H., Guido, T., Hu, K., Huang, J., Johnson-Wood, K., Khan, K., et al. (1999) · Nature · doi:10.1038/22124 · Cited by 3,160 · see citing works
Alzheimer's Disease: A Disorder of Cortical Cholinergic Innervation
Coyle, J. T., Price, D. L., & DeLong, M. R. (1983) · Science · doi:10.1126/science.6338589 · Cited by 3,050 · see citing works
Bard, F., Cannon, C., Barbour, R., Burke, R.-L., Games, D., Grajeda, H., Guido, T., Hu, K., Huang, J., Johnson-Wood, K., et al. (2000) · Nature Medicine · doi:10.1038/78682 · Cited by 2,012 · see citing works
Neurotrophic and Neurotoxic Effects of Amyloid β Protein: Reversal by Tachykinin Neuropeptides
Yankner, B. A., Duffy, L. K., & Kirschner, D. A. (1990) · Science · doi:10.1126/science.2218531 · Cited by 1,975 · see citing works
Alzheimer disease: Evidence for selective loss of cholinergic neurons in the nucleus basalis
Whitehouse, P. J., Price, D. L., Clark, A. W., Coyle, J. T., & DeLong, M. R. (1981) · Annals of Neurology · doi:10.1002/ana.410100203 · Cited by 1,736 · see citing works
Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP
Lewis, J., Dickson, D. W., Lin, W.-L., Chisholm, L., Corral, A., Jones, G., Yen, S.-H., Sahara, N., Skipper, L., Yager, D., et al. (2001) · Science · doi:10.1126/science.1058189 · Cited by 1,611 · see citing works
Translating cell biology into therapeutic advances in Alzheimer's disease
Selkoe, D. J. (1999) · Nature · doi:10.1038/399a023 · Cited by 1,588 · see citing works
Jankowsky, J. L., Fadale, D. J., Anderson, J., Xu, G. M., Gonzales, V., Jenkins, N. A., Copeland, N. G., Lee, M. K., Younkin, L. H., Wagner, S. L., et al. (2004) · Human Molecular Genetics · doi:10.1093/hmg/ddh019 · Cited by 1,575 · see citing works
Formation of Neurofibrillary Tangles in P301L Tau Transgenic Mice Induced by Aβ42 Fibrils
Götz, J., Chen, F., van Dorpe, J., & Nitsch, R. M. (2001) · Science · doi:10.1126/science.1062097 · Cited by 1,526 · see citing works
Aβ peptide vaccination prevents memory loss in an animal model of Alzheimer's disease
Morgan, D., Diamond, D. M., Gottschall, P. E., Ugen, K. E., Dickey, C. A., Hardy, J., Duff, K., Jantzen, P. T., DiCarlo, G., Wilcock, D. M., et al. (2000) · Nature · doi:10.1038/35050116 · Cited by 1,488 · see citing works
Aβ peptide immunization reduces behavioural impairment and plaques in a model of Alzheimer's disease
Janus, C., Pearson, J., McLaurin, J., Mathews, P. M., Jiang, Y., Schmidt, S. D., Chishti, M. A., Horne, P., Heslin, D., French, J., et al. (2000) · Nature · doi:10.1038/35050110 · Cited by 1,431 · see citing works
Holmes, C., Boche, D., Wilkinson, D., Yadegarfar, G., Hopkins, V., Bayer, A., Jones, R. W., Bullock, R., Love, S., Neal, J. W., et al. (2008) · The Lancet · doi:10.1016/s0140-6736(08)61075-2 · Cited by 1,416 · see citing works
Neuropathology of human Alzheimer disease after immunization with amyloid-β peptide: a case report
Nicoll, J. A. R., Wilkinson, D., Holmes, C., Steart, P., Markham, H., & Weller, R. O. (2003) · Nature Medicine · doi:10.1038/nm840 · Cited by 1,397 · see citing works
Asher, R. (1961) · The Lancet · doi:10.1016/s0140-6736(61)91217-x · Cited by 1,290 · see citing works
Neurotoxicity of a Fragment of the Amyloid Precursor Associated with Alzheimer's Disease
Yankner, B. A., Dawes, L. R., Fisher, S., Villa-Komaroff, L., Oster-Granite, M. L., & Neve, R. L. (1989) · Science · doi:10.1126/science.2474201 · Cited by 907 · see citing works
Raskind (2000) · doi:10.1212/wnl.54.12.2261 · Cited by 870 · see citing works
WAVE, a novel WASP‐family protein involved in actin reorganization induced by Rac
Miki, H., Suetsugu, S., & Takenawa, T. (1998) · The EMBO Journal · doi:10.1093/emboj/17.23.6932 · Cited by 709 · see citing works
Cholinergic modulation of microglial activation by α7 nicotinic receptors
Shytle, R. D., Mori, T., Townsend, K. P., Vendrame, M., Sun, N., Zeng, J., Ehrhart, J. C., Silver, A. A., Sanberg, P. R., & Tan, J. (2004) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2004.02347.x · Cited by 537 · see citing works
Selkoe (1999) · doi:10.1038/19866 · Cited by 468 · see citing works
Choline is a Selective Agonist of α7 Nicotinic Acetylcholine Receptors in the Rat Brain Neurons
Alkondon, M., Pereira, E. F. R., Cartes, W. S., Maelicke, A., & Albuquerque, E. X. (1997) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.1997.tb01702.x · Cited by 441 · see citing works
Self-citationKihara, T., Shimohama, S., Sawada, H., Honda, K., Nakamizo, T., Shibasaki, H., Kume, T., & Akaike, A. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m008035200 · Cited by 393 · see citing works
Self-citationSamochocki, M., Höffle‐Maas, A., Fehrenbacher, A., Jostock, R., Ludwig, J., Christner, C., Radina, M., Zerlin, M., Ullmer, C., Pereira, E. F. R., et al. (2003) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.102.045773 · Cited by 345 · see citing works
Self-citationMicroglial activation and amyloid‐β clearance induced by exogenous heat‐shock proteins
Kakimura, J., Kitamura, Y., Takata, K., Umeki, M., Suzuki, S., Shibagaki, K., Taniguchi, T., Nomura, Y., Gebicke‐Haerter, P. J., Smith, M. A., et al. (2002) · The FASEB Journal · doi:10.1096/fj.01-0530fje · Cited by 331 · see citing works
Self-citationOkamoto, K.-I., Narayanan, R., Lee, S. H., Murata, K., & Hayashi, Y. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0701656104 · Cited by 328 · see citing works
Maelicke, A., Samochocki, M., Jostock, R., Fehrenbacher, A., Ludwig, J., Albuquerque, E. X., & Zerlin, M. (2001) · Biological Psychiatry · doi:10.1016/s0006-3223(00)01109-4 · Cited by 303 · see citing works
Self-citationNicotinic receptor function: new perspectives from knockout mice
Cordero‐Erausquin, M., Marubio, L. M., Klink, R., & Changeux, J. (2000) · Trends in Pharmacological Sciences · doi:10.1016/s0165-6147(00)01489-9 · Cited by 295 · see citing works
Papke, R. L., Bencherif, M., & Lippiello, P. M. (1996) · Neuroscience Letters · doi:10.1016/0304-3940(96)12889-5 · Cited by 275 · see citing works
Suzuki, T., Hide, I., Matsubara, A., Hama, C., Harada, K., Miyano, K., Andrä, M., Matsubayashi, H., Sakai, N., Kohsaka, S., et al. (2006) · Journal of Neuroscience Research · doi:10.1002/jnr.20850 · Cited by 241 · see citing works
Schrattenholz, A. S., Pereira, E. F. R., Roth, U., Weber, K. H., Albuquerque, E. X., & Maelicke, A. (1996) · Molecular Pharmacology · doi:10.1016/s0026-895x(25)08675-4 · Cited by 226 · see citing works
Self-citationMaelicke, A., & Albuquerque, E. X. (2000) · European Journal of Pharmacology · doi:10.1016/s0014-2999(00)00093-5 · Cited by 222 · see citing works
Self-citationNordberg, A. K., Hellström‐Lindahl, E., Lee, M., Johnson, M. A., Mousavi, M. T., Hall, R., Perry, E. K., Bednar, I., & COURT, J. A. (2002) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2002.00874.x · Cited by 204 · see citing works
Amyloid-β Peptide Remnants in AN-1792-Immunized Alzheimer's Disease Patients
Patton, R., Kalback, W. M., Esh, C. L., Kokjohn, T. A., Vickle, G. D. V., Luehrs, D. C., Kuo, Y., Lopez, J. C., Brune, D. C., Ferrer, I., et al. (2006) · American Journal Of Pathology · doi:10.2353/ajpath.2006.060269 · Cited by 192 · see citing works
Raskind, M. A., Peskind, E. R., Truyen, L., Kershaw, P., & Damaraju, C. V. (2004) · Archives of Neurology · doi:10.1001/archneur.61.2.252 · Cited by 167 · see citing works
ALZHEIMER'S DISEASE AND RELATED DISORDERS
Raskind, M. A., & Peskind, E. R. (2001) · Medical Clinics of North America · doi:10.1016/s0025-7125(05)70341-2 · Cited by 161 · see citing works
Amyloid-β immunisation for Alzheimer's disease
Wisniewski, T., & Konietzko, U. (2008) · The Lancet Neurology · doi:10.1016/s1474-4422(08)70170-4 · Cited by 155 · see citing works
IL-4-Induced Selective Clearance of Oligomeric β-Amyloid Peptide1–42 by Rat Primary Type 2 Microglia
Shimizu, E., Kawahara, K., Kajizono, M., Sawada, M., & Nakayama, H. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.9.6503 · Cited by 143 · see citing works
Androgens modulate β‐amyloid levels in male rat brain
Ramsden, M., Nyborg, A. C., Murphy, M. P., Chang, L. J., Stanczyk, F. Z., Golde, T. E., & Pike, C. J. (2003) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2003.02114.x · Cited by 135 · see citing works
Nicotine reduces Aβ in the brain and cerebral vessels of APPsw mice
Hellström‐Lindahl, E., COURT, J. A., Keverne, J., Svedberg, M. M., Lee, M., Marutle, A., Thomas, A. J., Perry, E. K., Bednar, I., & Nordberg, A. K. (2004) · European Journal of Neuroscience · doi:10.1111/j.0953-816x.2004.03377.x · Cited by 127 · see citing works
Galantamine modulates nicotinic receptor and blocks Aβ-enhanced glutamate toxicity
Kihara, T., Sawada, H., Nakamizo, T., Kanki, R., Yamashita, H., Maelicke, A., & Shimohama, S. (2004) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2004.10.132 · Cited by 124 · see citing works
Self-citationMandelzys, A., Koninck, P. D., & Cooper, E. A. (1995) · Journal of Neurophysiology · doi:10.1152/jn.1995.74.3.1212 · Cited by 95 · see citing works
High mobility group box protein‐1 inhibits microglial Aβ clearance and enhances Aβ neurotoxicity
Takata, K., Kitamura, Y., Tsuchiya, D., Kawasaki, T., Taniguchi, T., & Shimohama, S. (2004) · Journal of Neuroscience Research · doi:10.1002/jnr.20340 · Cited by 81 · see citing works
Self-citationPhotoaffinity labeling of Torpedo acetylcholine receptor by physostigmine
Schrattenholz, A. S., Godovac‐Zimmermann, J., Schäfer, H., Albuquerque, E. X., & Maelicke, A. (1993) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1993.tb18187.x · Cited by 80 · see citing works
Self-citationLithner, C. U., Svedberg, M. M., Yu, W., Hedberg, M. M., & Nordberg, A. K. (2006) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.105.098566 · Cited by 59 · see citing works
Schröder, B., Reinhardt-Maelicke, S., Schrattenholz, A. S., McLane, K. E., Kretschmer, A., Conti-Tronconi, B. M., & Maelicke, A. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)34075-9 · Cited by 56 · see citing works
Self-citationKitamura, Y., Shibagaki, K., Takata, K., Tsuchiya, D., Taniguchi, T., Gebicke-Haerter, P. J., Miki, H., Takenawa, T., & Shimohama, S. (2003) · Journal of Pharmacological Sciences · doi:10.1254/jphs.92.115 · Cited by 39 · see citing works
Self-citationMaelicke, A., Coban, T., Storch, A., Schrattenholz, A. S., Pereira, E. F. R., & Albuquerque, E. X. (1997) · Journal of Receptors and Signal Transduction · doi:10.3109/10799899709036592 · Cited by 39 · see citing works
Self-citationTakata, K., Kitamura, Y., Nakata, Y., Matsuoka, Y., Tomimoto, H., Taniguchi, T., & Shimohama, S. (2009) · The American Journal of Pathology · doi:10.2353/ajpath.2009.080908 · Cited by 36 · see citing works
Self-citationHartmann, J., Kiewert, C., Duysen, E. G., Lockridge, O., & Klein, J. (2007) · Neurochemistry International · doi:10.1016/j.neuint.2007.10.008 · Cited by 33 · see citing works
Synergistic effect of galantamine on nicotine-induced neuroprotection in hemiparkinsonian rat model
Yanagida, T., Takeuchi, H., Kitamura, Y., Takata, K., Minamino, H., Shibaike, T., Tsushima, J., Kishimoto, K., Yasui, H., Taniguchi, T., et al. (2008) · Neuroscience Research · doi:10.1016/j.neures.2008.09.003 · Cited by 31 · see citing works
Self-citationTakata, K., Hirata‐Fukae, C., Becker, A. G., Chishiro, S., Gray, A. J., Nishitomi, K., Franz, A. H., Sakaguchi, G., Kato, A., Mattson, M. P., et al. (2007) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2007.05852.x · Cited by 29 · see citing works
Self-citationRegulation of platelet Rac1 and Cdc42 activation through interaction with calmodulin
Elsaraj, S. M., & Bhullar, R. P. (2008) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2008.01.022 · Cited by 27 · see citing works
Update on Alzheimer Drugs (Galantamine)
Raskind, M. A. (2003) · The Neurologist · doi:10.1097/01.nrl.0000087722.46430.c4 · Cited by 26 · see citing works
Expression of two neuronal nicotinic receptor subunits in innervated and denervated adult rat muscle
Sala, C., Kimura, I., Santoro, G., Kimura, M., & Fumagalli, G. F. (1996) · Neuroscience Letters · doi:10.1016/0304-3940(96)12923-2 · Cited by 21 · see citing works
Flagged first, then by citations
1 of the 60 references couldn’t be matched to a known paper.
Research works printed but not linked: 2
- Janus, C., Pearson, J., McLaurin, J., Mathews, P. M., Jiang, Y., Schmidt, S. D., Chishti, M. A., Horne, P., Heslin, D., French, J., Mount, H. T., Nixon, R. A., Mercken, M., Bergeron, C., Fraser, P. E., St George-Hyslop, P., and Westaway, D. (2000) Nature 408, 979 -982
- Okamoto, K., Narayanan, R., Lee, S. H., Murata, K., and Hayashi, Y. (2007) Proc. Natl. Acad. Sci. U.S.A. 104, 6418 -6423
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Neuroinflammation in neurodegenerative disorders: the roles of microglia and astrocytes
Kwon, H. S., & Koh, S.-H. (2020) · Translational Neurodegeneration · doi:10.1186/s40035-020-00221-2 · Cited by 2,595 · see citing works
Differential Roles of M1 and M2 Microglia in Neurodegenerative Diseases
Tang, Y., & Le, W. (2016) · Molecular Neurobiology · doi:10.1007/s12035-014-9070-5 · Cited by 2,190 · see citing works
Innate immunity in Alzheimer's disease
Heneka, M. T., Golenbock, D. T., & Latz, E. (2015) · Nature Immunology · doi:10.1038/ni.3102 · Cited by 902 · see citing works
The Gut Microbiota and Alzheimer’s Disease
Jiang, C., Li, G., Huang, P., Liu, Z., & Zhao, B. (2017) · Journal of Alzheimer's Disease · doi:10.3233/jad-161141 · Cited by 852 · see citing works
Bioinorganic Chemistry of Alzheimer’s Disease
Kepp, K. P. (2012) · Chemical Reviews · doi:10.1021/cr300009x · Cited by 672 · see citing works
Stansley, B., Post, J., & Hensley, K. (2012) · Journal of Neuroinflammation · doi:10.1186/1742-2094-9-115 · Cited by 419 · see citing works
Parsons, C. G., Danysz, W., Dekundy, A., & Pulte, I. (2013) · Neurotoxicity Research · doi:10.1007/s12640-013-9398-z · Cited by 337 · see citing works
Anti-inflammatory role of microglial alpha7 nAChRs and its role in neuroprotection
Egea, J., Buendía, I., Parada, E., Navarro, E., Leon, R. M., & López, M. G. (2015) · Biochemical Pharmacology · doi:10.1016/j.bcp.2015.07.032 · Cited by 299 · see citing works
The biological pathways of Alzheimer disease: a review
Calabrò, M., Rinaldi, C., Santoro, G., & Crisafulli, C. (2020) · AIMS neuroscience · doi:10.3934/neuroscience.2021005 · Cited by 271 · see citing works
Inhibitors of Acetylcholinesterase and Butyrylcholinesterase Meet Immunity
Pohanka, M. (2014) · International Journal of Molecular Sciences · doi:10.3390/ijms15069809 · Cited by 248 · see citing works
Alzheimer’s disease as an inflammatory disease
Bolós, M., Perea, J. R., & Avila, J. (2017) · BioMolecular Concepts · doi:10.1515/bmc-2016-0029 · Cited by 216 · see citing works
Research update: Alpha7 nicotinic acetylcholine receptor mechanisms in Alzheimer's disease
Parri, H. R., Hernandez, C. M., & Dineley, K. T. (2011) · Biochemical Pharmacology · doi:10.1016/j.bcp.2011.06.039 · Cited by 199 · see citing works
Ahmad, M. H., Fatima, M., & Mondal, A. C. (2018) · Journal of Clinical Neuroscience · doi:10.1016/j.jocn.2018.10.034 · Cited by 193 · see citing works
Cholinergic System and Its Therapeutic Importance in Inflammation and Autoimmunity
Halder, N., & Lal, G. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.660342 · Cited by 186 · see citing works
Modulatory effects of α7 nAChRs on the immune system and its relevance for CNS disorders
Kalkman, H. O., & Feuerbach, D. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-016-2175-4 · Cited by 182 · see citing works
Jiang, Y., Li, K., Li, X., Xu, L., & Yang, Z. (2021) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2021.109452 · Cited by 154 · see citing works
Bhattacharya, S., Haertel, C., Maelicke, A., & Montag, D. (2014) · PLoS ONE · doi:10.1371/journal.pone.0089454 · Cited by 142 · see citing works
Self-citationMisra, S., Chopra, K., Sinha, V. R., & Medhi, B. (2016) · Drug Delivery · doi:10.3109/10717544.2015.1089956 · Cited by 136 · see citing works
β-Amyloid and the Pathomechanisms of Alzheimer’s Disease: A Comprehensive View
Penke, B., Bogár, F., & Fülöp, L. (2017) · Molecules · doi:10.3390/molecules22101692 · Cited by 135 · see citing works
Cholinergic Modulation of Glial Function During Aging and Chronic Neuroinflammation
Gamage, R. V., Wagnon, I. M., Rossetti, I., Childs, R., Niedermayer, G., Chesworth, R., & Gyengési, E. (2020) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.577912 · Cited by 133 · see citing works
Moreira, N. C. D. S., Lima, J. E. B. D. F., Marchiori, M. F., Carvalho, I., & Sakamoto‐Hojo, E. T. (2022) · Journal of Alzheimer s Disease Reports · doi:10.3233/adr-210061 · Cited by 132 · see citing works
Kawamata, J., & Shimohama, S. (2011) · Journal of Alzheimer's Disease · doi:10.3233/jad-2011-110173 · Cited by 111 · see citing works
Self-citationBenfante, R., Lascio, S. D., Cardani, S., & Fornasari, D. (2019) · Aging Clinical and Experimental Research · doi:10.1007/s40520-019-01359-4 · Cited by 100 · see citing works
Microglial Function in the Effects of Early-Life Stress on Brain and Behavioral Development
Catale, C., Gironda, S. C., Iacono, L. L., & Carola, V. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9020468 · Cited by 99 · see citing works
A novel cell line from spontaneously immortalized murine microglia
Nagamoto‐Combs, K., Kulas, J. A., & Combs, C. K. (2014) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2014.05.021 · Cited by 95 · see citing works
Atanasova, M., Stavrakov, G., Philipova, I., Zheleva, D., Yordanov, N., & Doytchinova, I. A. (2015) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2015.07.058 · Cited by 94 · see citing works
Han, B., Li, X., & Hao, J. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2017.04.002 · Cited by 96 · see citing works
Zueva, I. V., Dias, J., Lushchekina, S. V., Semenov, V. E., Mukhamedyarov, M. A., Pashirova, T. N., Babaev, V. M., Nachon, F., Petrova, N. V., Faritovich, N. L., et al. (2019) · Neuropharmacology · doi:10.1016/j.neuropharm.2019.05.025 · Cited by 91 · see citing works
Echeverrı́a, V., Iarkov, A., & Aliev, G. (2016) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2016.01.002 · Cited by 91 · see citing works
Multitarget drugs of plants origin acting on Alzheimer’s disease
Russo, P., Frustaci, A., Del Bufalo, A., Fini, M., & Cesario, A. (2013) · Current Medicinal Chemistry · doi:10.2174/0929867311320130008 · Cited by 88 · see citing works
The role of astrocytic α7 nicotinic acetylcholine receptors in Alzheimer disease
Fontana, I. C., Kumar, A., & Nordberg, A. (2023) · Nature Reviews Neurology · doi:10.1038/s41582-023-00792-4 · Cited by 86 · see citing works
Wazea, S. A., Wadie, W., Bahgat, A. K., & El-Abhar, H. S. (2018) · Scientific Reports · doi:10.1038/s41598-018-23359-6 · Cited by 79 · see citing works
Anwar, S., & Rivest, S. (2020) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2020.1738391 · Cited by 78 · see citing works
Toward a Rational Design to Regulate β-Amyloid Fibrillation for Alzheimer’s Disease Treatment
Han, X., & He, G. (2017) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.7b00477 · Cited by 77 · see citing works
Galantamine-Memantine combination in the treatment of Alzheimer's disease and beyond
Koola, M. M. (2020) · Psychiatry Research · doi:10.1016/j.psychres.2020.113409 · Cited by 76 · see citing works
Nanotechnology to improve the Alzheimer’s disease therapy with natural compounds
Ramalho, M. J., Andrade, S., Loureiro, J. A., & do Carmo Pereira, M. (2020) · Drug Delivery and Translational Research · doi:10.1007/s13346-019-00694-3 · Cited by 75 · see citing works
Microglia as Dynamic and Essential Components of the Amyloid Hypothesis
Gandy, S., & Heppner, F. L. (2013) · Neuron · doi:10.1016/j.neuron.2013.05.007 · Cited by 73 · see citing works
An update on drug treatment options of Alzheimer's disease
Allgaier, M. (2014) · Frontiers in bioscience · doi:10.2741/4285 · Cited by 69 · see citing works
Effects of galantamine in a 2-year, randomized, placebo-controlled study in Alzheimer's disease
Baseman, A. S., Häger, K., Nye, J. S., Brashear, R. H., Han, J., Sano, M., Davis, B. M., & Richards, H. M. (2014) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s57909 · Cited by 69 · see citing works
Takata, K., Amamiya, T., Mizoguchi, H., Kawanishi, S., Kuroda, E., Kitamura, R., Ito, A., Saito, Y., Tawa, M., Nagasawa, T., et al. (2017) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2017.10.021 · Cited by 67 · see citing works
Self-citationAntioxidant Activity of Galantamine and Some of its Derivatives
Tsvetkova, D. D., Obreshkova, D. P., Zheleva‐Dimitrova, D., & Saso, L. (2013) · Current Medicinal Chemistry · doi:10.2174/09298673113209990148 · Cited by 65 · see citing works
Shang, J., Yamashita, T., Zhai, Y., Nakano, Y., Morihara, R., Fukui, Y., Hishikawa, N., Ohta, Y., & Abe, K. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-151126 · Cited by 64 · see citing works
Xu, Y., Au, N. P. B., & Ma, C. H. E. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.896852 · Cited by 63 · see citing works
Neurotoxicity evoked by organophosphates and available countermeasures
Pulkrabkova, L., Svobodová, B., Konecny, J., Kobrlová, T., Múčková, Ľ., Janousek, J., Pejchal, J., Korábečný, J., & Soukup, O. (2022) · Archives of Toxicology · doi:10.1007/s00204-022-03397-w · Cited by 63 · see citing works
Nicotinic Acetylcholine Receptor Signaling in Neuroprotection
Akaike, A., Shimohama, S., & Misu, Y. (2018) · Springer eBooks · doi:10.1007/978-981-10-8488-1 · Cited by 60 · see citing works
Self-citationTakata, K., Takada, T., Ito, A., Asai, M., Tawa, M., Saito, Y., Ashihara, E., Tomimoto, H., Kitamura, Y., & Shimohama, S. (2012) · International Journal of Alzheimer s Disease · doi:10.1155/2012/685739 · Cited by 58 · see citing works
Self-citationMohamed, L. A., Qosa, H., & Kaddoumi, A. (2015) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.5b00040 · Cited by 58 · see citing works
Antidiabetic Effect of Galantamine: Novel Effect for a Known Centrally Acting Drug
Ali, M. A., El-Abhar, H. S., Kamel, M. A. E.-N., & Attia, A. S. (2015) · PLoS ONE · doi:10.1371/journal.pone.0134648 · Cited by 56 · see citing works
Sadigh‐Eteghad, S., Majdi, A., Mahmoudi, J., Golzari, S. E., & Talebi, M. (2016) · Journal of Neural Transmission · doi:10.1007/s00702-016-1580-z · Cited by 53 · see citing works
Importance of GPCR-Mediated Microglial Activation in Alzheimer’s Disease
Haque, M. E., Kim, I., Jakaria, M., Akther, M., & Choi, D. (2018) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2018.00258 · Cited by 55 · see citing works
Gao, J., Inagaki, Y., Li, X., Kokudo, N., & Tang, W. (2013) · Drug Discoveries & Therapeutics · doi:10.5582/ddt.2013.v7.2.46 · Cited by 52 · see citing works
Formulation and Evaluation of Galantamine Gel as Drug Reservoir in Transdermal Patch Delivery System
Woo, F.-Y., Basri, M., Ahmad, M. B., & Ismail, M. (2015) · The Scientific World JOURNAL · doi:10.1155/2015/495271 · Cited by 51 · see citing works
Yokokawa, K., Iwahara, N., Hisahara, S., Emoto, M. C., Saito, T., Suzuki, H., Manabe, T., Matsumura, A., Matsushita, T., Suzuki, S., et al. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-190817 · Cited by 48 · see citing works
Self-citationKawanishi, S., Takata, K., Itezono, S., Nagayama, H., Konoya, S., Chisaki, Y., Toda, Y., Nakata, S., Yano, Y., Kitamura, Y., et al. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-170994 · Cited by 47 · see citing works
Self-citationNeuroinflammation Modulation via α7 Nicotinic Acetylcholine Receptor and Its Chaperone, RIC-3
Mizrachi, T., Vaknin‐Dembinsky, A., Brenner, T., & Treinin, M. (2021) · Molecules · doi:10.3390/molecules26206139 · Cited by 46 · see citing works
Galantamine-Curcumin Hybrids as Dual-Site Binding Acetylcholinesterase Inhibitors
Stavrakov, G., Philipova, I., Lukarski, A., Atanasova, M., Zheleva‐Dimitrova, D., Zhivkova, Z. D., Ivanov, S. M., Atanasova, T., Konstantinov, S., & Doytchinova, I. A. (2020) · Molecules · doi:10.3390/molecules25153341 · Cited by 44 · see citing works
Saito, T., Hisahara, S., Iwahara, N., Emoto, M. C., Yokokawa, K., Suzuki, H., Manabe, T., Matsumura, A., Suzuki, S., Matsushita, T., et al. (2019) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2019.09.014 · Cited by 42 · see citing works
Self-citationMicroglial Phagocytosis—Rational but Challenging Therapeutic Target in Multiple Sclerosis
Pinto, M. V., & Fernandes, A. M. A. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21175960 · Cited by 41 · see citing works
Shen, Y., Zhao, M., Zhao, P., Meng, L., Zhang, Y., Zhang, G., Taishi, Y., & Sun, L. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2024.1408462 · Cited by 42 · see citing works
Takata, K., Ginhoux, F., & Shimohama, S. (2021) · Biochemical Pharmacology · doi:10.1016/j.bcp.2021.114754 · Cited by 40 · see citing works
Self-citationMorioka, N., Tokuhara, M., Nakamura, Y., Idenoshita, Y., Harano, S., Zhang, F. F., Hisaoka‐Nakashima, K., & Nakata, Y. (2013) · Neuroscience · doi:10.1016/j.neuroscience.2013.11.044 · Cited by 39 · see citing works
Bhattacharya, S., Maelicke, A., & Montag, D. (2015) · Journal of Alzheimer s Disease · doi:10.3233/jad-142421 · Cited by 39 · see citing works
Self-citationURMC-099 facilitates amyloid-β clearance in a murine model of Alzheimer’s disease
Kiyota, T., Machhi, J., Lu, Y., Dyavarshetty, B., Nemati, M., Zhang, G., Mosley, R. L., Gelbard, H. A., & Gendelman, H. E. (2018) · Journal of Neuroinflammation · doi:10.1186/s12974-018-1172-y · Cited by 38 · see citing works
Dey, A., & Mukherjee, A. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-809593-5.00006-9 · Cited by 39 · see citing works
Signaling of nicotinic acetylcholine receptors in mononuclear phagocytes
Richter, K., & Grau, V. (2023) · Pharmacological Research · doi:10.1016/j.phrs.2023.106727 · Cited by 39 · see citing works
The dialog between neurons and microglia in Alzheimer's disease: The neurotransmitters view
Stolero, N., & Frenkel, D. (2020) · Journal of Neurochemistry · doi:10.1111/jnc.15262 · Cited by 37 · see citing works
Calcium ion influx in microglial cells: Physiological and therapeutic significance
Sharma, P., & Ping, L. (2014) · Journal of Neuroscience Research · doi:10.1002/jnr.23344 · Cited by 37 · see citing works
Molecular Docking Study on Galantamine Derivatives as Cholinesterase Inhibitors
Atanasova, M., Yordanov, N., Dimitrov, I., Berkov, S. H., & Doytchinova, I. A. (2015) · Molecular Informatics · doi:10.1002/minf.201400145 · Cited by 36 · see citing works
Galantamine attenuates amyloid-β deposition and astrocyte activation in APP/PS1 transgenic mice
Wu, Z., Zhao, L., Chen, X., Cheng, X., & Zhang, Y. (2015) · Experimental Gerontology · doi:10.1016/j.exger.2015.10.015 · Cited by 36 · see citing works
Autism - A Neurodevelopmental Journey from Genes to Behaviour
Eapen, V. (2011) · InTech eBooks · doi:10.5772/974 · Cited by 36 · see citing works
Fujikura, M., Iwahara, N., Hisahara, S., Kawamata, J., Matsumura, A., Yokokawa, K., Saito, T., Manabe, T., Matsushita, T., Suzuki, S., et al. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-180904 · Cited by 35 · see citing works
Self-citationRegulation of microglia by neuromodulators: Modulations in major and minor modes
Albertini, G., Etienne, F., & Roumier, A. (2020) · Neuroscience Letters · doi:10.1016/j.neulet.2020.135000 · Cited by 35 · see citing works
Nicotinic acetylcholine receptors mediate donepezil‐induced oligodendrocyte differentiation
Imamura, O., Arai, M., Dateki, M., Ogata, T., Uchida, R., Tomoda, H., & Takishima, K. (2015) · Journal of Neurochemistry · doi:10.1111/jnc.13294 · Cited by 35 · see citing works
Takata, K., & Kitamura, Y. (2012) · Journal of Pharmacological Sciences · doi:10.1254/jphs.11r10fm · Cited by 34 · see citing works
Self-citationIwahara, N., Hisahara, S., Kawamata, J., Matsumura, A., Yokokawa, K., Saito, T., Fujikura, M., Manabe, T., Suzuki, H., Matsushita, T., et al. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-160887 · Cited by 34 · see citing works
Self-citationShang, J., Yamashita, T., Zhai, Y., Nakano, Y., Morihara, R., Li, X., Tian, F., Liu, X., Huang, Y. C., Shi, X., et al. (2018) · Neuroscience Research · doi:10.1016/j.neures.2018.06.002 · Cited by 33 · see citing works
Stavrakov, G., Philipova, I., Zheleva‐Dimitrova, D., Valkova, I., Salamanova, E., Konstantinov, S., & Doytchinova, I. A. (2017) · Chemical Biology & Drug Design · doi:10.1111/cbdd.12991 · Cited by 32 · see citing works
Li, L., Li, L., Zhang, J., Huang, S., Liu, W., Wang, Z., Liang, S., Tao, J., & Chen, L. (2020) · Neural Plasticity · doi:10.1155/2020/8836173 · Cited by 32 · see citing works
Simeonova, R., Zheleva‐Dimitrova, D., Valkova, I., Stavrakov, G., Philipova, I., Atanasova, M., & Doytchinova, I. A. (2021) · Molecules · doi:10.3390/molecules26071865 · Cited by 32 · see citing works
Decourt, B., Noorda, K., Noorda, K. J., Shi, J., & Sabbagh, M. N. (2022) · Journal of Experimental Pharmacology · doi:10.2147/jep.s265626 · Cited by 32 · see citing works
Easton, A. E., Sankaranarayanan, S., Tanghe, A., Terwel, D., Lin, A., Hoque, N., Bourin, C., Gu, H., Ahlijanian, M. K., & Bristow, L. J. (2013) · Psychopharmacology · doi:10.1007/s00213-013-3152-3 · Cited by 32 · see citing works
Lane, R. M., & Darreh‐Shori, T. (2015) · Journal of Alzheimer s Disease · doi:10.3233/jad-142268 · Cited by 31 · see citing works
Rajkumar, M., Sakthivel, M., Senthilkumar, K., Thangaraj, R., & Kannan, S. (2022) · Current Research in Pharmacology and Drug Discovery · doi:10.1016/j.crphar.2022.100100 · Cited by 29 · see citing works
Atta, A. A., Ibrahim, W. W., Mohamed, A. F., & Abdelkader, N. F. (2023) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2023.175810 · Cited by 29 · see citing works
El-Ganainy, S. O., Gowayed, M. A., Agami, M. A., Mohamed, P., Belal, M., Farid, R. M., & Hanafy, A. S. (2021) · Nanomedicine · doi:10.2217/nnm-2021-0051 · Cited by 28 · see citing works
Chrysanthou, M., Estruch, I. M., Rietjens, I. M. C. M., Wichers, H. J., & Hoppenbrouwers, T. (2022) · Nutrients · doi:10.3390/nu14020363 · Cited by 29 · see citing works
Takata, K., Kimura, H., Yanagisawa, D., Harada, K., Nishimura, K., Kitamura, Y., Shimohama, S., & Tooyama, I. (2022) · Molecules · doi:10.3390/molecules27092780 · Cited by 29 · see citing works
Self-citationThe mixed-lineage kinase 3 inhibitor URMC-099 facilitates microglial amyloid-β degradation
Dong, W., Embury, C. M., Lu, Y., Whitmire, S. M., Dyavarshetty, B., Gelbard, H. A., Gendelman, H. E., & Kiyota, T. (2016) · Journal of Neuroinflammation · doi:10.1186/s12974-016-0646-z · Cited by 28 · see citing works
Shimohama, S., & Kawamata, J. (2018) · Springer eBooks · doi:10.1007/978-981-10-8488-1_8 · Cited by 29 · see citing works
Self-citationSteiner, L., Gold, M., Mengel, D., Dodel, R. C., & Bach, J. (2014) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2014.06.032 · Cited by 27 · see citing works
Docking-based Design of Galantamine Derivatives with Dual-site Binding to Acetylcholinesterase
Stavrakov, G., Philipova, I., Zheleva‐Dimitrova, D., Atanasova, M., Konstantinov, S., & Doytchinova, I. A. (2016) · Molecular Informatics · doi:10.1002/minf.201600041 · Cited by 27 · see citing works
Diagnoses of Pathological States Based on Acetylcholinesterase and Butyrylcholinesterase
Pohanka, M. (2019) · Current Medicinal Chemistry · doi:10.2174/0929867326666190130161202 · Cited by 26 · see citing works
Targeted drug delivery systems to control neuroinflammation in central nervous system disorders
Mozafari, N., Ashrafi, H., & Azadi, A. (2021) · Journal of Drug Delivery Science and Technology · doi:10.1016/j.jddst.2021.102802 · Cited by 25 · see citing works
Complexity of Sex Differences and Their Impact on Alzheimer’s Disease
Kadlecová, M., Freude, K., & Haukedal, H. (2023) · Biomedicines · doi:10.3390/biomedicines11051261 · Cited by 26 · see citing works
Kuroda, E., Nishimura, K., Kawanishi, S., Sueyoshi, M., Ueno, F., Toji, Y., Abo, N., Konishi, T., Harada, K., Satake, S., et al. (2020) · Neuroscience · doi:10.1016/j.neuroscience.2020.05.004 · Cited by 24 · see citing works
Self-citationMorioka, N., Harano, S., Tokuhara, M., Idenoshita, Y., Zhang, F. F., Hisaoka‐Nakashima, K., & Nakata, Y. (2015) · Brain Research · doi:10.1016/j.brainres.2015.08.029 · Cited by 24 · see citing works
Liu, S.-Z., Cheng, W., Shao, J.-W., Gu, Y.-F., Zhu, Y., Dong, Q.-J., Bai, S., Wang, P., & Li, L. (2019) · Current Medical Science · doi:10.1007/s11596-019-2019-1 · Cited by 23 · see citing works
Nakamura, Y., Kimura, S., Takada, N., Takemura, M., Iwamoto, M., Hisaoka‐Nakashima, K., Nakata, Y., & Morioka, N. (2020) · Neurochemistry International · doi:10.1016/j.neuint.2020.104751 · Cited by 22 · see citing works
Liu, N., Haziyihan, A., Zhao, W. G., Chen, Y., & Chao, H. (2024) · Translational Neurodegeneration · doi:10.1186/s40035-024-00434-9 · Cited by 21 · see citing works
Donepezil suppresses intracellular Ca2+ mobilization through the PI3K pathway in rodent microglia
Haraguchi, Y., Mizoguchi, Y., Ohgidani, M., Imamura, Y., Murakawa‐Hirachi, T., Nabeta, H., Tateishi, H., Kato, T. A., & Monji, A. (2017) · Journal of Neuroinflammation · doi:10.1186/s12974-017-1033-0 · Cited by 22 · see citing works
- Authors
- Takata, K., Kitamura, Y., Saeki, M., Terada, M., Kagitani, S., Kitamura, R., Fujikawa, Y., Maelicke, A., Tomimoto, H., Taniguchi, T., & Shimohama, S.
- Affiliations
- Kyoto Pharmaceutical University (JP)
- Mie University (JP)
- Sapporo Medical University (JP)
- Corresponding author
- Kitamura, Yoshihisa
- Shimohama, Shun
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2010-12
- Volume
- 285
- Issue
- 51
- Pages
- 40180-40191
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC3001000
- OpenAlex
- W2022036412
- Cited by
- 176
- References
- 60
- Citations by year
- 2026: 7 · 2025: 11 · 2024: 7 · 2023: 11 · 2022: 10 · 2021: 12 · 2020: 16 · 2019: 13 · 2018: 11 · 2017: 13 · 2016: 16 · 2015: 16 · 2014: 8 · 2013: 12 · 2012: 6
- FWCI
- 5.20
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Keywords
- galantamine, amyloid-beta clearance, microglia, alpha7 nicotinic acetylcholine receptor, choline, calcium influx, actin reorganization, calmodulin signaling, Alzheimer's disease, microglial phagocytosis
- MeSH terms
- Aged, Alzheimer Disease, Animals, Antibodies, Monoclonal, Binding Sites, Calmodulin, Cells, Cultured, Choline, Cholinesterase Inhibitors, Disease Models, Animal, Female, Galantamine, Hippocampus, Humans, Male, Phagocytosis, Receptors, Nicotinic, Amyloid beta-Peptides, Rats, Wistar, Microglia, Nootropic Agents, Calcium Signaling, Rats
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