glycogen synthase kinase
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2023 ◽  
Vol 83 ◽  
Author(s):  
A. Ullah ◽  
N. Ali ◽  
S. Ahmad ◽  
S. U. Rahman ◽  
S. Alghamdi ◽  
...  

Abstract Diabetes mellitus (DM) is a non-communicable disease throughout the world in which there is persistently high blood glucose level from the normal range. The diabetes and insulin resistance are mainly responsible for the morbidities and mortalities of humans in the world. This disease is mainly regulated by various enzymes and hormones among which Glycogen synthase kinase-3 (GSK-3) is a principle enzyme and insulin is the key hormone regulating it. The GSK-3, that is the key enzyme is normally showing its actions by various mechanisms that include its phosphorylation, formation of protein complexes, and other cellular distribution and thus it control and directly affects cellular morphology, its growth, mobility and apoptosis of the cell. Disturbances in the action of GSK-3 enzyme may leads to various disease conditions that include insulin resistance leading to diabetes, neurological disease like Alzheimer’s disease and cancer. Fluoroquinolones are the most common class of drugs that shows dysglycemic effects via interacting with GSK-3 enzyme. Therefore, it is the need of the day to properly understand functions and mechanisms of GSK-3, especially its role in glucose homeostasis via effects on glycogen synthase.


2022 ◽  
Author(s):  
Samuel Pazicky ◽  
Arne Alder ◽  
Haydyn Mertens ◽  
Dmitri I. Svergun ◽  
Tim Gilberger ◽  
...  

As the decline of malaria cases stalled over the last five years, novel targets in Plasmodium falciparum are necessary for the development of new drugs. Glycogen Synthase Kinase (PfGSK3) has been identified as a potential target, since its selective inhibitors were shown to disrupt the parasite's life cycle. In the uncanonical N‑terminal region of the parasite enzyme, we identified several autophosphorylation sites and probed their role in activity regulation of PfGSK3. By combining molecular modeling with experimental small-angle X-ray scattering data, we show that increased PfGSK3 activity is promoted by conformational changes in the PfGSK3 N‑terminus, triggered by N‑terminal phosphorylation. Our work provides novel insights into the structure and regulation of the malarial PfGSK3.


2022 ◽  
Vol 524 ◽  
pp. 259-267
Author(s):  
Roland Houben ◽  
Sonja Hesbacher ◽  
Bhavishya Sarma ◽  
Carolin Schulte ◽  
Eva-Maria Sarosi ◽  
...  

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Ling Li ◽  
Tian Li ◽  
Xin Tian ◽  
Ling Zhao

Objective. Ginseng is a plant of the family Acanthopanaceae. It has been used for thousands of years in China. It is known as the king of hundred herbs. It was recorded first in Shennong Baicao Jing. It has been found that ginsenoside Rd is a neuroprotective agent. This article aims to explore the protective roles of ginsenoside Rd in Alzheimer’s disease. Rd, a Chinese herb, may be a promising treatment drug for Alzheimer’s disease (AD) and is also reported to be related to several pathological changes, including the deposition of Aβ and tau hyperphosphorylation in AD as it decreases the deposition of tau hyperphosphorylation in APP transgenic mice. Methods. In this study, APP transgenic mice were pretreated with 10 mg/kg Rd for six months, and the effect of Rd on neuropathological deficits in the olfactory bulb, spinal cord, and telencephalon of APP transgenic mice was investigated. The phosphorylation levels of tau (S199/202, S396, S404, and Tau5) and the activities of the proteins glycogen synthase kinase 3β (Tyr216) and cyclin-dependent kinase 5 (P25/P35) were measured. Results. The pretreatment of Rd effectively decreased the production and deposition of hyperphosphorylated tau (S199/202, S396, and S404) protein by depressing the expression of glycogen synthase kinase 3β (GSK-3β/Tyr216) and cyclin-dependent kinase 5 (CDK5/P25). Conclusion. These findings suggest that ginsenoside Rd could improve the pathological changes of AD in the olfactory bulb, spinal cord, and telencephalon, which further demonstrated the potential therapeutic effect of Rd in early AD.


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