Atm and c-Abl cooperate in the response to genotoxic stress during nervous system development

Miller, Heather Lee; Lee, Youngsoo; Zhao, Jingfeng; Chong, Miriam J.; McKinnon, Peter J.

doi:10.1016/s0165-3806(03)00192-5

Cited by 7 publications

(3 citation statements)

References 37 publications

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“…In addition to its typical functions in the pathogenesis of leukemia, c-Abl is also considered to play an important role in neuronal development, neuronal migration, axon extension and synaptic plasticity [37][38][39]. Miller et al found that c-Abl and ataxia-telangiectasia mutation (ATM) are very important for development and survival, especially after genotoxic stress, and that they have obvious selectivity for the developing nervous system [50]. In addition, c-Abl functionally interacts with p53 during cell development, and mice lacking them are unlikely to be viable [51].…”

Section: Neuronal Cell Developmentmentioning

confidence: 99%

Roles for c-Abl in postoperative neurodegeneration

Feng¹,

Fu²,

Yao³

et al. 2022

Int. J. Med. Sci.

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The nonreceptor tyrosine kinase c-Abl is inactive under normal conditions. Upon activation, c-Abl regulates signaling pathways related to cytoskeletal reorganization. It plays a vital role in modulating cell protrusion, cell migration, morphogenesis, adhesion, endocytosis and phagocytosis. A large number of studies have also found that abnormally activated c-Abl plays an important role in a variety of pathologies, including various inflammatory diseases and neurodegenerative diseases. c-Abl also plays a crucial role in neurodevelopment and neurodegenerative diseases, mainly through mechanisms such as neuroinflammation, oxidative stress (OS), and Tau protein phosphorylation. Inhibiting expression or activity of this kinase has certain neuroprotective and anti-inflammatory effects and can also improve cognition and behavior. Blockers of this kinase may have good preventive and treatment effects on neurodegenerative diseases. Cognitive dysfunction after anesthesia is also closely related to the abovementioned mechanisms. We infer that alterations in the expression and activity of c-Abl may underlie postoperative cognitive dysfunction (POCD). This article summarizes the current understanding and research progress on the mechanisms by which c-Abl may be related to postoperative neurodegeneration.

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Section: Neuronal Cell Developmentmentioning

confidence: 99%

Roles for c-Abl in postoperative neurodegeneration

Feng¹,

Fu²,

Yao³

et al. 2022

Int. J. Med. Sci.

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“…ATM expression primarily in the CNS has been noted in Xenopus embryo [ 138 ] as well as in adult mouse and humans [ 139 , 140 ]. Previously documented is the crucial role of ATM in eliminating neural cells with DNA damage [ 139 , 141 - 143 ] through the apoptotic pathway [ 135 ].…”

Section: Radioprotectors: Df-1 and Amifostinementioning

confidence: 99%

Zebrafish as a Model System to Screen Radiation Modifiers

Hwang¹,

Yong²,

Moretti³

et al. 2007

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Zebrafish (Danio rerio) is a bona fide vertebrate model system for understanding human diseases. It allows the transparent visualization of the effects of ionizing radiation and the convenient testing of potential radioprotectors with morpholino-modified oligonucleotides (MO) knockdown. Furthermore, various reverse and forward genetic methods are feasible to decipher novel genetic modifiers of radioprotection. Examined in the review are the radioprotective effects of the proposed radiomodifiers Nanoparticle DF-1 (C-Sixty, Inc., Houston, TX) and Amifostine (WR-2721, Ethyol), the DNA repair proteins Ku80 and ATM, as well as the transplanted hematopoietic stem cells in irradiated zebrafish. The presence of any of these sufficiently rescued the radiation-induced damages in zebrafish, while its absence resulted in mutagenic phenotypes as well as an elevation of time-and dose-dependent radiation-induced apoptosis. Radiosensitizers Flavopiridol and AG1478, both of which block progression into the radioresistant S phase of the cell cycle, have also been examined in zebrafish. Zebrafish has indeed become a favorite model system to test for radiation modifiers that can potentially be used for radiotherapeutic purposes in humans. I. ZEBRAFISH AS AN IDEAL MODEL SYSTEMZebrafish (Danio rerio) has been envisioned as a popular vertebrate model system for studying radioprotection. The extensive forward genetic screens in the 1990s initiated the study of genes affecting zebrafish embryonic development [1,2], and since then a large number of zebrafish mutants exhibiting rare human diseases have been obtained. Recent studies on zebrafish as a model system have provided important insight into various human diseases of oncogenic, neurodegenerative, hematopoietic, and cardiovascular origin [3][4][5][6]. Despite the evolutionary divergence nearly 450 million years ago, the human and zebrafish genome exhibit considerable homology with the conservation of key genes involved in development, signal transduction, cell cycle progression and proliferation, and cell differentiation [7][8][9][10][11]. The effects of ionizing radiation on the two organisms and the extent of phenotypic rescue by radioprotective substances are also similar.Most importantly, zebrafish offers far more practical benefits as a laboratory model system than any other organism. At low cost and with ease of care, large numbers of zebrafish can be maintained in a small space wherein frequent paired matings produce hundreds of embryos at a time. Its optical transparency of embryos allows the visualization of major organ systems during the rapid 3 months of embryonic development. Within 48 hours postfertilization (hpf), major organ systems such as the eyes, brain, heart, liver, muscles, bones, and the GI tract are evident. External embryogenesis also allows experimental manipulations to be conveniently carried out without parental sacrifice. Genetic manipulations *Address correspondence to this author at the Department of Radiation Oncology, Vanderbilt University,...

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“…Atm-null in a DNA-PK null-mutant background or the dual inactivation of Atm and c-Abl [a target of Atm kinase]) [7 ,41]. The presence of one allele of Atm or c-Abl enables the double mutant embryos to survive but, after radiation, they display an increased incidence of exencephaly (see Glossary) and eye malformations [41]. Rad9, a checkpoint control gene product, is phosphorylated by Atm and c-Abl.…”

Section: Signaling and Regulation Of Dna Repairmentioning

confidence: 99%

DNA repair disorders causing malformations

Hales

2005

Current Opinion in Genetics & Development

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Atm and c-Abl cooperate in the response to genotoxic stress during nervous system development

Cited by 7 publications

References 37 publications

Roles for c-Abl in postoperative neurodegeneration

Roles for c-Abl in postoperative neurodegeneration

Zebrafish as a Model System to Screen Radiation Modifiers

DNA repair disorders causing malformations

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