Enzyme glycogen synthase kinase-3 (GSK-3) is a candidate pharmacological target for the treatment of neurodegenerative diseases of the brain. Given the many molecular, cellular, and functional features shared by the brain and the retina in both physiological and pathological processes, drugs originally designed to treat neurodegenerative diseases of the brain could be useful candidates for the treatment of retinal degenerative pathologies. Moreover, the accessibility of the eye to noninvasive, quantitative diagnostic techniques allows for easier evaluation of the efficacy of candidate therapies in clinical trials. In this chapter, we discuss the potential of GSK-3 inhibitors in the treatment of retinal degeneration.
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http://dx.doi.org/10.1007/978-3-030-27378-1_72 | DOI Listing |
Drug Des Devel Ther
January 2025
Department of Anesthesiology, The Affiliated Hospital of Qingdao University, Qingdao, People's Republic of China.
Introduction: The mechanism of remimazolam, a benzodiazepine that activates γ-aminobutyric acid a (GABAa) receptors, in cerebral ischemia/reperfusion (I/R) injury is not well understood. Therefore, we explored whether remimazolam activates protein kinase B (AKT)/glycogen synthase kinase-3β (GSK-3β)/nuclear factor erythroid 2-related factor 2 (NRF2) to attenuate brain I/R injury in transcerebral I/R-injured rats and transoxygenic glucose deprivation/reperfusion (OGD/R)-injured SY5Y cells.
Material And Methods: Remimazolam was added at the beginning of cell and rat reperfusion, and the PI3K/AKT inhibitor LY294002 was added to inhibit the AKT/GSK-3β/NRF2 pathway 24 h before cellular OGD/R treatment and 30 min before rat brain I/R treatment.
Endocr Metab Immune Disord Drug Targets
January 2025
Department of Endocrinology, Jiangyin Hospital Affiliated to Nanjing University of Chinese Medicine, No. 130 Renmin Middle Road, Jiangyin City, Jiangsu Province, 214413, China.
Introduction: Berberine (BBR) has the characteristics of repressing hyperglycemia, obesity, and inflammation, as well as improving insulin resistance. However, the underlying mechanism remains to be fully understood. This study explores whether BBR regulates inositol requiring enzyme 1 (IRE1)/glycogen synthase kinase 3 beta (GSK-3β) axis to resist obesity-associated inflammation, thereby improving glucolipid metabolism disorders.
View Article and Find Full Text PDFCell Commun Signal
January 2025
Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China.
Cognitive impairment is a significant complication of type 2 diabetes mellitus (T2DM). However, the mechanisms underlying the development of cognitive dysfunction in individuals with T2DM remain elusive. Herein, we discussed the role of Bmal1, a core circadian rhythm-regulating gene, in the process of T2DM-associated cognitive dysfunction.
View Article and Find Full Text PDFExp Mol Med
January 2025
Cancer Centre, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR, China.
FHIT is a fragile site tumor suppressor that is primarily inactivated upon tobacco smoking. FHIT loss is frequently observed in lung cancer, making it an important biomarker for the development of targeted therapy for lung cancer. Here, we report that inhibitors of glycogen synthase kinase 3 beta (GSK3β) and the homologous recombination DNA repair (HRR) pathway are synthetic lethal with FHIT loss in lung cancer.
View Article and Find Full Text PDFSci Rep
January 2025
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ahram Canadian University, Giza, Egypt.
Unlabelled: Despite the fact that canagliflozin (Cana), a sodium-glucose cotransporter 2 inhibitor, is an anti-diabetic medication with additional effects on the kidney, there is limited experimental data to deliberate its hepato-reno-protective potentiality. Acetaminophen (APAP) overdose remains one of the prominent contributors to hepato-renal damage.
Aim: Our study assessed the novel effect of Cana against APAP-induced toxicities.
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