Activation of the neuronal c-Abl tyrosine kinase by amyloid-β-peptide and reactive oxygen species
Open accessAbstract
The deposition and accumulation of amyloid-beta-peptide (Abeta) in the brain are considered a sine qua non for Alzheimer's disease. The experimental delivery of fibrilized Abeta serves as a cellular model for several facets of the disease including the induction of synaptic dysfunction and apoptosis. c-Abl kinase is involved in the regulation of apoptosis and its pro-apoptotic function is in part mediated by its interaction with p73, a p53 homologue. We found that c-Abl activation is involved in cell signals that regulate neuronal death response to Abeta fibrils. Abeta peptide fibrils induced an increase of the c-Abl activity in rat hippocampal neurons as well as an increase in nuclear p73 protein levels and the p73-c-Abl complex. The neuronal cell death induced by Abeta fibrils was prevented by the inhibition of c-Abl with imatinib mesylate (Gleevec or STI571) and by the inhibition c-Abl expression by RNAi. These results directly point to a therapeutic strategy for the treatment of Alzheimer's disease.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
c-Abl has been identified as an important pathogenic mediator of neurodegenerative diseases.
“Since c-Abl has been identified as an important pathogenic mediator of neurodegenerative diseases (Alvarez et al., 2004; Imam et al., 2011; Jing et al., 2009; Ko et al., 2010; Schlatterer et al., 2011)”
From Nilotinib restores memory function by preventing dopaminergic neuron degeneration in a mouse model of Alzheimer’s Disease (2021) · cites this paper as Alvarez et al., 2004
The observation of an increase in c-Abl phosphorylation in Tg2576 mice is consistent with other studies that identify c-Abl as a pathogenesis mediator in AD.
“c-Abl is an important regulator of the autophagic process (Abushouk et al., 2018) and of other pathways that set the choice between survival and cell death, thus the observation of an increase in c-Abl phosphorylation in Tg2576 mice is consistent with other studies that identify c-Abl as a pathogenesis mediator in AD (Alvarez et al., 2004; Jing et al., 2009).”
From Nilotinib restores memory function by preventing dopaminergic neuron degeneration in a mouse model of Alzheimer’s Disease (2021) · cites this paper as Alvarez et al., 2004
Cites
Mosmann, T. (1983) · Journal of Immunological Methods · doi:10.1016/0022-1759(83)90303-4 · Cited by 56,104 · 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
Andrews, N. C., & Faller, D. V. (1991) · Nucleic Acids Research · doi:10.1093/nar/19.9.2499 · Cited by 2,337 · see citing works
Apoptosis in the nervous system
Yuan, J., & Yankner, B. A. (2000) · Nature · doi:10.1038/35037739 · Cited by 1,862 · see citing works
APP Processing and Synaptic Function
Kamenetz, F., Tomita, T., Hsieh, H., Seabrook, G., Borchelt, D., Iwatsubo, T., Sisodia, S., & Malinow, R. (2003) · Neuron · doi:10.1016/s0896-6273(03)00124-7 · Cited by 1,644 · see citing works
Apoptosis in neurodegenerative disorders
Mattson, M. P. (2000) · Nature Reviews Molecular Cell Biology · doi:10.1038/35040009 · Cited by 1,605 · see citing works
Glivec (STI571, imatinib), a rationally developed, targeted anticancer drug
Capdeville, R., Buchdunger, E., Zimmermann, J., & Matter, A. (2002) · Nature Reviews Drug Discovery · doi:10.1038/nrd839 · Cited by 1,391 · see citing works
The tyrosine kinase c-Abl regulates p73 in apoptotic response to cisplatin-induced DNA damage
Gong, J., Costanzo, A., Yang, H., Melino, G., Kaelin, W. G., Levrero, M., & Wang, J. Y. J. (1999) · Nature · doi:10.1038/21690 · Cited by 923 · see citing works
p73 is regulated by tyrosine kinase c-Abl in the apoptotic response to DNA damage
Yuan, Z.-M., Shioya, H., Ishiko, T., Sun, X., Gu, J., Huang, Y., Lu, H., Kharbanda, S. M., Weichselbaum, R. W., & Kufe, D. W. (1999) · Nature · doi:10.1038/21704 · Cited by 574 · see citing works
Interaction of c-Abl and p73α and their collaboration to induce apoptosis
Agami, R., Blandino, G., Oren, M., & Shaul, Y. (1999) · Nature · doi:10.1038/21697 · Cited by 544 · see citing works
p63 and p73: p53 mimics, menaces and more
Yang, A., & McKeon, F. (2000) · Nature Reviews Molecular Cell Biology · doi:10.1038/35043127 · Cited by 504 · see citing works
On the shoulders of giants: p63, p73 and the rise of p53
Yang, A., Kaghad, M., Caput, D., & McKeon, F. (2002) · Trends in Genetics · doi:10.1016/s0168-9525(02)02595-7 · Cited by 486 · see citing works
An Anti-Apoptotic Role for the p53 Family Member, p73, During Developmental Neuron Death
Pozniak, C. D., Radinovic, S., Yang, A., McKeon, F., Kaplan, D. R., & Miller, F. D. (2000) · Science · doi:10.1126/science.289.5477.304 · Cited by 465 · see citing works
Weisberg, E., & Griffin, J. D. (2000) · Blood · doi:10.1182/blood.v95.11.3498 · Cited by 398 · see citing works
Essential Roles for the Abl and Arg Tyrosine Kinases in Neurulation
Koleske, A. J., Gifford, A. M., Scott, M. L., Nee, M., Bronson, R. T., Miczek, K. A., & Baltimore, D. (1998) · Neuron · doi:10.1016/s0896-6273(00)80646-7 · Cited by 397 · see citing works
Human ΔNp73 regulates a dominant negative feedback loop for TAp73 and p53
Grob, T. J., Novak, U., Maisse, C., Barcaroli, D., Lüthi, A. U., Pirnia, F., Hügli, B., Graber, H. U., Laurenzi, V. D., Fey, M. F., et al. (2001) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4400962 · Cited by 340 · see citing works
Cycling, stressed-out and nervous: cellular functions of c-Abl
Etten, R. A. V. (1999) · Trends in Cell Biology · doi:10.1016/s0962-8924(99)01549-4 · Cited by 321 · see citing works
Alvarez, A. R., Alarcón, R., Opazo, C., Campos, E. O., Muñoz, F. J., Calderón, F. H., Dajas, F., Gentry, M. K., Doctor, B. P., Mello, F. G. D., et al. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-09-03213.1998 · Cited by 320 · see citing works
Self-citationMAP2 is localized to the dendrites of hippocampal neurons which develop in culture
Cáceres, A., Banker, G. A., Steward, O., Binder, L. I., & Payne, M. R. (1984) · Developmental Brain Research · doi:10.1016/0165-3806(84)90167-6 · Cited by 320 · see citing works
Integrin regulation of c-Abl tyrosine kinase activity and cytoplasmic–nuclear transport
Lewis, J. M., Rajasekaran, B., Taagepera, S., Schwartz, M. A., & Wang, J. Y. J. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.26.15174 · Cited by 311 · see citing works
Atwood, C., Obrenovich, M. E., Liu, T., Chan, H., Perry, G. L., Smith, M. A., & Martins, R. N. (2003) · Brain Research Reviews · doi:10.1016/s0165-0173(03)00174-7 · Cited by 292 · see citing works
Brasher, B. B., & Etten, R. A. V. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m005401200 · Cited by 278 · see citing works
Regulation of cell death by the Abl tyrosine kinase
Wang, J. Y. J. (2000) · Oncogene · doi:10.1038/sj.onc.1203878 · Cited by 278 · see citing works
Pluk, H., Dorey, K., & Superti‐Furga, G. (2002) · Cell · doi:10.1016/s0092-8674(02)00623-2 · Cited by 249 · see citing works
Inhibition of tau phosphorylating protein kinase cdk5 prevents β‐amyloid‐induced neuronal death
Alvarez, A. R., Toro, R., Cáceres, A., & Maccioni, R. B. (1999) · FEBS Letters · doi:10.1016/s0014-5793(99)01279-x · Cited by 228 · see citing works
Self-citationCrude extracts of bacterially expressed dsRNA can be used to protect plants against virus infections
Tenllado, F., Martínez‐García, B., Vargas, M., et al. (2003) · BMC Biotechnology · doi:10.1186/1472-6750-3-3 · Cited by 214 · see citing works
The mouse c-abl locus: Molecular cloning and characterization
Wang, J. Y. J., Ledley, F. D., Goff, S. P., Lee, R., Groner, Y., & Baltimore, D. (1984) · Cell · doi:10.1016/0092-8674(84)90228-9 · Cited by 199 · see citing works
Gleevec inhibits β-amyloid production but not Notch cleavage
Netzer, W. J., Dou, F., Cai, D., Veach, D. R., Jean, S., Li, Y., Bornmann, W. G., Clarkson, B., Xu, H., & Greengard, P. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1534745100 · Cited by 192 · see citing works
Activation of the repulsive receptor Roundabout inhibits N-cadherin-mediated cell adhesion
Rhee, J., Mahfooz, N. S., Arregui, C. O., Lilien, J. E., Balsamo, J., & VanBerkum, M. F. A. (2002) · Nature Cell Biology · doi:10.1038/ncb858 · Cited by 183 · see citing works
Activation of the Cytoplasmic c-Abl Tyrosine Kinase by Reactive Oxygen Species
Sun, X., Majumder, P. K., Shioya, H., Wu, F., Kumar, S., Weichselbaum, R. R., Kharbanda, S. M., & Kufe, D. W. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.c000099200 · Cited by 167 · see citing works
Determination of cell fate by c-Abl activation in the response to DNA damage
Kharbanda, S. M., Yuan, Z.-M., Weichselbaum, R. W., & Kufe, D. W. (1998) · Oncogene · doi:10.1038/sj.onc.1202571 · Cited by 166 · see citing works
How do Abl family kinases regulate cell shape and movement?
Hernández, S. E., Krishnaswami, M., Miller, A. L., & Koleske, A. J. (2003) · Trends in Cell Biology · doi:10.1016/j.tcb.2003.11.003 · Cited by 165 · see citing works
Woodring, P. J., Litwack, E. D., O’Leary, D. D. M., Lucero, G. R., Wang, J. Y. J., & Hunter, T. R. (2002) · The Journal of Cell Biology · doi:10.1083/jcb.200110014 · Cited by 164 · see citing works
p73 Is Required for Survival and Maintenance of CNS Neurons
Pozniak, C. D., Barnabé‐Heider, F., Rymar, V. V., Lee, A. F., Sadikot, A. F., & Miller, F. D. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-22-09800.2002 · Cited by 146 · see citing works
Two Distinct Phosphorylation Pathways Have Additive Effects on Abl Family Kinase Activation
Tanis, K. Q., Veach, D. R., Duewel, H. S., et al. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.11.3884-3896.2003 · Cited by 143 · see citing works
c-Abl: activation and nuclear targets
Shaul, Y. (2000) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4400626 · Cited by 138 · see citing works
A new link between the c-Abl tyrosine kinase and phosphoinositide signalling through PLC-γ1
Plattner, R., Irvin, B. J., Guo, S., et al. (2003) · Nature Cell Biology · doi:10.1038/ncb949 · Cited by 126 · see citing works
Kumar, S., Bharti, A. K., Mishra, N. C., Raina, D., Kharbanda, S. M., Saxena, S. P., & Kufe, D. W. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m101414200 · Cited by 108 · see citing works
c-Abl stabilizes p73 by a phosphorylation-augmented interaction.
Tsai, K. K., & Yuan, Z.-M. (2003) · PubMed · Cited by 95 · see citing works
Cbl-ArgBP2 complex mediates ubiquitination and degradation of c-Abl
Soubeyran, P., Barac, A., Szymkiewicz, I., & Đikić, I. (2003) · Biochemical Journal · doi:10.1042/bj20021539 · Cited by 69 · see citing works
Baskaran, R., Escobar, S. R., & Wang, J. Y. J. (1999) · PubMed · Cited by 67 · see citing works
Abl Family Nonreceptor Tyrosine Kinases Modulate Short-Term Synaptic Plasticity
Moresco, E. M. Y., Scheetz, A. J., Bornmann, W. G., Koleske, A. J., & Fitzsimonds, R. M. (2003) · Journal of Neurophysiology · doi:10.1152/jn.00892.2002 · Cited by 61 · see citing works
Kumar, S., Mishra, N. C., Raina, D., Saxena, S. P., & Kufe, D. W. (2003) · Molecular Pharmacology · doi:10.1124/mol.63.2.276 · Cited by 57 · see citing works
Lu, Q., Mukhopadhyay, N. K., Griffin, J. D., Paredes, M. F., Medina, M., & Kosik, K. S. (2002) · Journal of Neuroscience Research · doi:10.1002/jnr.10151 · Cited by 51 · see citing works
Self-citationRequirement of caspase-mediated cleavage of c-Abl during stress-induced apoptosis
Machuy, N., Rajalingam, K., & Rudel, T. (2003) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401336 · Cited by 49 · see citing works
c-Abl Tyrosine Kinase Selectively Regulates p73 Nuclear Matrix Association
Ben‐Yehoyada, M., Ben‐Dor, I., & Shaul, Y. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m301051200 · Cited by 47 · see citing works
Wilson, C., Henry, S. E., Smith, M. A., & Bowser, R. P. (2003) · Neuropathology and Applied Neurobiology · doi:10.1046/j.0305-1846.2003.00496.x · Cited by 37 · see citing works
Wang, J. Y. J., & Ki, S. W. (2001) · Biochemical Society Transactions · doi:10.1042/bst0290666 · Cited by 33 · see citing works
Homo- and hetero-oligomerization of the c-Abl kinase and Abelson-interactor-1.
Fan, P., Cong, F., & Goff, S. P. (2003) · PubMed · Cited by 27 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Tebay, L. E., Robertson, H., Durant, S. T., Vitale, S. R., Penning, T. M., Dinkova-Kostova, A. T., & Hayes, J. D. (2015) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2015.06.021 · Cited by 837 · see citing works
Tau protein kinases: Involvement in Alzheimer's disease
Martin, L., Latypova, X., Wilson, C. M., Magnaudeix, A., Perrin, M.-L., Yardin, C., & Terro, F. (2013) · Ageing Research Reviews · doi:10.1016/j.arr.2012.06.003 · Cited by 631 · see citing works
Karuppagounder, S. S., Brahmachari, S., Lee, Y., Dawson, V. L., Dawson, T. M., & Ko, H. S. (2014) · Scientific Reports · doi:10.1038/srep04874 · Cited by 264 · see citing works
Tau Protein Interaction Partners and Their Roles in Alzheimer’s Disease and Other Tauopathies
Sinsky, J., Pichlerova, K., & Hanes, J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22179207 · Cited by 220 · see citing works
Lonskaya, I., Hebron, M. L., Desforges, N. M., Schachter, J. B., & Moussa, C. E.-H. (2014) · Journal of Molecular Medicine · doi:10.1007/s00109-013-1112-3 · Cited by 152 · see citing works
The DNA Damage Response in Neurons: Die by Apoptosis or Survive in a Senescence-Like State?
Fielder, E., von Zglinicki, T., & Jurk, D. (2017) · Journal of Alzheimer's Disease · doi:10.3233/jad-161221 · Cited by 126 · see citing works
c-Abl tyrosine kinase modulates tau pathology and Cdk5 phosphorylation in AD transgenic mice
Cancino, G. I., Perez de Arce, K., Castro, P. U., Toledo, E. M., von Bernhardi, R., & Alvarez, A. R. (2011) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2009.07.007 · Cited by 110 · see citing works
La Barbera, L., Vedele, F., Nobili, A., Krashia, P., Spoleti, E., Latagliata, E. C., Cutuli, D., Cauzzi, E., Marino, R., Viscomi, M. T., et al. (2021) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2021.102031 · Cited by 98 · see citing works
“…et al., 2018) and of other pathways that set the choice between survival and cell death, thus the observation of an increase in c-Abl phosphorylation in Tg2576 mice is consistent with other studies that identify c-Abl as a pathogenesis mediator in AD (Alvarez et al., 2004; Jing et al., 2009).”
BackgroundResultEnhancing autophagy in Alzheimer's disease through drug repositioning
Eshraghi, M., Ahmadi, M., Afshar, S., Lorzadeh, S., Adlimoghaddam, A., Rezvani Jalal, N., West, R., Dastghaib, S., Igder, S., Torshizi, S. R. N., et al. (2022) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2022.108171 · Cited by 89 · see citing works
Altered subcellular distribution of c-Abl in Alzheimer’s disease
Jing, Z., Caltagarone, J., & Bowser, R. (2009) · Journal of Alzheimer s Disease · doi:10.3233/jad-2009-1062 · Cited by 83 · see citing works
Oxidative stress, DNA damage, and c-Abl signaling: At the crossroad in neurodegenerative diseases?
Gonfloni, S., Maiani, E., Di Bartolomeo, C., Diederich, M., & Cesareni, G. (2012) · International Journal of Cell Biology · doi:10.1155/2012/683097 · Cited by 63 · see citing works
Targeting dementias through cancer kinases inhibition
Fagiani, F., Lanni, C., Racchi, M., & Govoni, S. (2020) · Alzheimer's & Dementia: Translational Research & Clinical Interventions · doi:10.1002/trc2.12044 · Cited by 43 · see citing works
Reduction of apoptosis in Rb-deficient embryos via Abl knockout
Borges, H. L., Hunton, I. C., & Wang, J. Y. J. (2007) · Oncogene · doi:10.1038/sj.onc.1210157 · Cited by 14 · see citing works
Protein kinase inhibitors as therapeutics in neurodegenerative and psychiatric disorders
Tridente, G., Jana, A., Nath, A., & Ashraf, G. M. (2023) · Receptor Tyrosine Kinases in Neurodegenerative and Psychiatric Disorders · doi:10.1016/b978-0-443-18677-6.00015-4 · Cited by 8 · see citing works
Mansour, H. M. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102195 · Cited by 3 · see citing works
- Authors
- Alvarez, A. R., Sandoval, P. C., Leal, N. R., Castro, P. U., & Kosik, K. S.
- Affiliations
- Pontificia Universidad Católica de Chile (CL)
- Brigham and Women's Hospital (US)
- Corresponding author
- Alvarez, Alejandra R.
- Venue
- Neurobiology of Disease
- Publisher
- Elsevier BV
- Published
- 2004-11
- Volume
- 17
- Issue
- 2
- Pages
- 326-336
- ISSN
- 0969-9961 (ISSN-L)
- OpenAlex
- W2018105735
- Cited by
- 125
- References
- 49
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 4 · 2023: 7 · 2022: 8 · 2021: 8 · 2020: 7 · 2019: 5 · 2018: 3 · 2017: 6 · 2016: 7 · 2015: 4 · 2014: 7 · 2013: 6 · 2012: 8
- FWCI
- 1.23
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- Neurobiology of Disease (publishedVersion)
- PubMed (publishedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (publishedVersion, other-oa)
- Americanae (AECID Library) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Fondo de Financiamiento de Centros de Investigación en Áreas Prioritarias
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- c-Abl kinase, amyloid-beta, reactive oxygen species, Alzheimer's disease, neuronal apoptosis, p73, imatinib mesylate, hippocampal neurons, kinase activation, RNA interference, treatment options
- MeSH terms
- Tumor Protein p73, Amyloid, Animals, Cells, Cultured, DNA-Binding Proteins, Embryo, Mammalian, Enzyme Activation, Hippocampus, Neurons, Nuclear Proteins, Up-Regulation, Genes, Tumor Suppressor, Amyloid beta-Peptides, Proto-Oncogene Proteins c-abl, Cell Death, Rats, Sprague-Dawley, Apoptosis, Reactive Oxygen Species, Oxidative Stress, Tumor Suppressor Proteins, 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
