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Details on Person Many GSK-3β inhibitors (GSKi) have been identified. They are...
| Class:Id | Summation:9687779 |
|---|---|
| _displayName | Many GSK-3β inhibitors (GSKi) have been identified. They are... |
| _timestamp | 2021-10-08 13:31:19 |
| created | [InstanceEdit:9687759] Stephan, Ralf, 2020-05-12 |
| literatureReference | [LiteratureReference:9687723] GSK-3 as potential target for therapeutic intervention in cancer [LiteratureReference:9687775] Glycogen synthase kinase-3 and cancer: good cop, bad cop? [LiteratureReference:9687772] Glycogen synthase kinase-3 inhibitors augment TRAIL-induced apoptotic death in human hepatoma cells [LiteratureReference:9687721] Glycogen synthase kinase 3 in MLL leukaemia maintenance and targeted therapy [LiteratureReference:9687760] Selective GSK-3beta inhibitors attenuate the cisplatin-induced cytotoxicity of auditory cells [LiteratureReference:9687740] Lithium inhibits glycogen synthase kinase-3 by competition for magnesium [LiteratureReference:9687764] A longitudinal study of the effects of lithium treatment on prefrontal and subgenual prefrontal gray matter volume in treatment-responsive bipolar disorder patients [LiteratureReference:9755444] Targeting the coronavirus nucleocapsid protein through GSK-3 inhibition |
| modified | [InstanceEdit:9729580] Stephan, Ralf, 2021-04-29 [InstanceEdit:9755457] Stephan, Ralf, 2021-10-08 |
| text | Many GSK-3β inhibitors (GSKi) have been identified. They are known to induce apoptosis in leukemia and pancreatic cancer cells, and can destabilize p53, which may promote cellular death in response to DNA damaging agents (Wang et al, 2008; Beurel et al, 2009). Administration of GSKi inhibited cochlear destruction in cisplatin-injected mice (Park et al, 2009). Lithium is a selective ATP competitive inhibitor of GSK-3 (Ryves and Harwood, 2001). Lithium carbonate is used with bipolar disorder patients (Moore et al, 2009). In a retrospective study of 162,118 COVID-19 patients from several U.S. health systems 7% of patients taking lithium developed COVID-19 compared with 15% among the general population (Liu et al, 2021). LY2090314 has been in clinical trials for metastatic pancreatic cancer and acute leukemia ([NCT01632306], [NCT01287520], [NCT01214603]). Clinical trials of GSKi for Alzheimer's disease were unsuccessful. The use of GSKi remains controversial because of their possibly oncogenic properties. Evaluation of GSKi in clinical trials has been hampered by the fear that inhibition of GSK-3 may stimulate or aid in malignant transformation as GSK-3 can phosphorylate pro-oncogenic factors such as beta-catenin, c-Jun and c-Myc which targets them for degradation (Patel & Woodgett, 2008). However, no studies have been reported suggesting that treatment of mice with GSKi resulted in an increase in cancer incidence. In fact, many patients with bipolar disorder have been treated with lithium for prolonged periods of time, with no evidence that these patients have increased incidences of cancer (McCubrey et al, 2014). The GSKi kenpaullone and lithium chloride were found to reduce viral Nucleoprotein phosphorylation in the severe acute respiratory syndrome CoV-infected VeroE6 cells and decrease the viral titer and cytopathic symptoms. Effects of GSK-3 inhibition were reproduced in another coronavirus, the neurotropic JHM strain of mouse hepatitis virus (Wu et al, 2009). |
| (summation) | [Reaction:9687724] GSK3B binds GSKi [Homo sapiens] |
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