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
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
