The DOI matches its Crossref record; 59 of the 60 references it cites were found in a registry or an index.
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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]
In the citing paper
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
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
Massagué, J. (1998) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.67.1.753 · Cited by 7,571
Rho GTPases and the Actin Cytoskeleton
Hall, A. (1998) · Science · doi:10.1126/science.279.5350.509 · Cited by 6,138
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
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
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
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
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 3,052
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
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
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
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
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
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
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 1,506
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
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
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
Asher, R. (1961) · The Lancet · doi:10.1016/s0140-6736(61)91217-x · Cited by 1,293
Translating cell biology into therapeutic advances in Alzheimer's disease
Selkoe, D. J. (1999) · Nature · doi:10.1038/399a023 · Cited by 1,166
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
Raskind (2000) · doi:10.1212/wnl.54.12.2261 · Cited by 870
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 705
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
Selkoe (1999) · doi:10.1038/19866 · Cited by 468
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 440
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 412
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
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 333
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
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
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
Papke, R. L., Bencherif, M., & Lippiello, P. M. (1996) · Neuroscience Letters · doi:10.1016/0304-3940(96)12889-5 · Cited by 275
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 247
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
Self-citationMaelicke, A., & Albuquerque, E. X. (2000) · European Journal of Pharmacology · doi:10.1016/s0014-2999(00)00093-5 · Cited by 224
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
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 195
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
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
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
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
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
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
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
Self-citationMandelzys, A., Koninck, P. D., & Cooper, E. A. (1995) · Journal of Neurophysiology · doi:10.1152/jn.1995.74.3.1212 · Cited by 95
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 82
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
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
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
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
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
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
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
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
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
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
Update on Alzheimer Drugs (Galantamine)
Raskind, M. A. (2003) · The Neurologist · doi:10.1097/01.nrl.0000087722.46430.c4 · Cited by 26
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
Cited by
Sorted by citations
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
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
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
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
Bioinorganic Chemistry of Alzheimer’s Disease
Kepp, K. P. (2012) · Chemical Reviews · doi:10.1021/cr300009x · Cited by 683
Metadata
- 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
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
