scholarly journals The Role of GSK3 in Presynaptic Function

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Karen Janet Smillie ◽  
Michael Alan Cousin
Keyword(s):  
Synaptic Vesicles ◽  
Glycogen Synthase ◽  
Glycogen Synthase Kinase 3 ◽  
Nerve Terminals ◽  
The Past ◽  
Presynaptic Function ◽  
Signalling Cascades ◽  
Synaptic Failure ◽  
Activity Dependent

The past ten years of research have identified a number of key roles for glycogen synthase kinase 3 (GSK3) at the synapse. In terms of presynaptic physiology, critical roles for GSK3 have been revealed in the growth and maturation of the nerve terminal and more recently a key role in the control of activity-dependent bulk endocytosis of synaptic vesicles. This paper will summarise the major roles assigned to GSK3 in both immature and mature nerve terminals, the substrates GSK3 phosphorylates to exert its action, and how GSK3 activity is regulated by different presynaptic signalling cascades. The number of essential roles for GSK3, coupled with the numerous signalling cascades all converging to regulate its activity, suggests that GSK3 is a key integrator of multiple inputs to modulate the strength of neurotransmission. Modulation of these pathways may point to potential mechanisms to overcome synaptic failure in neurodegenerative disorders such as Alzheimer's disease.

scholarly journals THE ORGANIZATION AND INNERVATION OF THE LUMINESCENT ORGAN IN A FIREFLY, PHOTURIS PENNSYLVANICA (COLEOPTERA)

1963 ◽  
Vol 16 (2) ◽  
pp. 323-359 ◽  
Author(s):  
David S. Smith
Keyword(s):  
Electron Microscope ◽  
Synaptic Vesicles ◽  
Light Emission ◽  
Nerve Endings ◽  
Tracheal Epithelium ◽  
Nerve Terminals ◽  
Tracheal System ◽  
Physiological Evidence ◽  
Effector System

The organization of the luminescent organ of an adult firefly has been studied with the electron microscope, and particular attention has been given to the disposition of nerve terminals within the organ. The cytological structure of the cells of the tracheal system, the peripheral and terminal axons, the photocytes and the cells of the dorsal ("reflecting") layer is described. Previous observations on the peripheral course of nerve branches alongside the tracheal trunks at the level of the dorsal layer and photocyte epithelium have been confirmed, and specialised nerve endings containing axoplasmic components structurally identical with "synaptic vesicles" and "neurosecretory droplets" have been identified, not in association with the surface of the photocytes, but lying between the apposed surfaces of two components of the tracheal epithelium: the tracheal end-cell and the tracheolar cell. These cytological findings are discussed in terms of available biochemical and physiological evidence concerning the mechanism of light emission in the firefly, especially with respect to the possible role of chemical "transmitter" action in triggering a response in a luminescent effector system.

scholarly journals Erratum to: A Crosstalk between the Biorhythms and Gatekeepers of Longevity: Dual Role of Glycogen Synthase Kinase-3

2021 ◽  
Vol 86 (5) ◽  
pp. 611-611
Author(s):  
Gregory A. Shilovsky ◽  
Tatyana S. Putyatina ◽  
Galina V. Morgunova ◽  
Alexander V. Seliverstov ◽  
Vasily V. Ashapkin ◽  
...  
Keyword(s):  
Glycogen Synthase ◽  
Dual Role ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3

scholarly journals Possible Role of the Glycogen Synthase Kinase-3 Signaling Pathway in Trimethyltin-Induced Hippocampal Neurodegeneration in Mice

PLoS ONE ◽  
2013 ◽  
Vol 8 (8) ◽  
pp. e70356 ◽  
Author(s):  
Juhwan Kim ◽  
Miyoung Yang ◽  
Sung-Ho Kim ◽  
Jong-Choon Kim ◽  
Hongbing Wang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Glycogen Synthase ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3 ◽  
Hippocampal Neurodegeneration

scholarly journals Deletion of Cardiomyocyte Glycogen Synthase Kinase-3 Beta (GSK-3β) Improves Systemic Glucose Tolerance with Maintained Heart Function in Established Obesity

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1120 ◽  
Author(s):  
Manisha Gupte ◽  
Prachi Umbarkar ◽  
Anand Prakash Singh ◽  
Qinkun Zhang ◽  
Sultan Tousif ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Cardiac Function ◽  
Cardiac Dysfunction ◽  
Glycogen Synthase ◽  
Critical Role ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3 ◽  
Total Period ◽  
Gsk 3Β

Obesity is an independent risk factor for cardiovascular diseases (CVD), including heart failure. Thus, there is an urgent need to understand the molecular mechanism of obesity-associated cardiac dysfunction. We recently reported the critical role of cardiomyocyte (CM) Glycogen Synthase Kinase-3 beta (GSK-3β) in cardiac dysfunction associated with a developing obesity model (deletion of CM-GSK-3β prior to obesity). In the present study, we investigated the role of CM-GSK-3β in a clinically more relevant model of established obesity (deletion of CM-GSK-3β after established obesity). CM-GSK-3β knockout (GSK-3βfl/flCre+/−) and controls (GSK-3βfl/flCre−/−) mice were subjected to a high-fat diet (HFD) in order to establish obesity. After 12 weeks of HFD treatment, all mice received tamoxifen injections for five consecutive days to delete GSK-3β specifically in CMs and continued on the HFD for a total period of 55 weeks. To our complete surprise, CM-GSK-3β knockout (KO) animals exhibited a globally improved glucose tolerance and maintained normal cardiac function. Mechanistically, in stark contrast to the developing obesity model, deleting CM-GSK-3β in obese animals did not adversely affect the GSK-3αS21 phosphorylation (activity) and maintained canonical β-catenin degradation pathway and cardiac function. As several GSK-3 inhibitors are in the trial to treat various chronic conditions, including metabolic diseases, these findings have important clinical implications. Specifically, our results provide critical pre-clinical data regarding the safety of GSK-3 inhibition in obese patients.

scholarly journals GSK3α: An Important Paralog in Neurodegenerative Disorders and Cancer

Biomolecules ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 1683
Author(s):  
Octavio Silva-García ◽  
Ricarda Cortés-Vieyra ◽  
Francisco N. Mendoza-Ambrosio ◽  
Guillermo Ramírez-Galicia ◽  
Víctor M. Baizabal-Aguirre
Keyword(s):  
Neurodegenerative Disorders ◽  
Glycogen Synthase ◽  
Similar Efficacy ◽  
Glycogen Synthase Kinase 3 ◽  
Brain Functions ◽  
Chemical Inhibitors ◽  
Simultaneous Inhibition ◽  
The Brain

The biological activity of the enzyme glycogen synthase kinase-3 (GSK3) is fulfilled by two paralogs named GSK3α and GSK3β, which possess both redundancy and specific functions. The upregulated activity of these proteins is linked to the development of disorders such as neurodegenerative disorders (ND) and cancer. Although various chemical inhibitors of these enzymes restore the brain functions in models of ND such as Alzheimer’s disease (AD), and reduce the proliferation and survival of cancer cells, the particular contribution of each paralog to these effects remains unclear as these molecules downregulate the activity of both paralogs with a similar efficacy. Moreover, given that GSK3 paralogs phosphorylate more than 100 substrates, the simultaneous inhibition of both enzymes has detrimental effects during long-term inhibition. Although the GSK3β kinase function has usually been taken as the global GSK3 activity, in the last few years, a growing interest in the study of GSK3α has emerged because several studies have recognized it as the main GSK3 paralog involved in a variety of diseases. This review summarizes the current biological evidence on the role of GSK3α in AD and various types of cancer. We also provide a discussion on some strategies that may lead to the design of the paralog-specific inhibition of GSK3α.

scholarly journals Identification of a novel selective and potent inhibitor of glycogen synthase kinase-3

2019 ◽  
Vol 317 (6) ◽  
pp. C1289-C1303 ◽  
Author(s):  
Mahboubeh S. Noori ◽  
Pooja M. Bhatt ◽  
Maria C. Courreges ◽  
Davoud Ghazanfari ◽  
Chaz Cuckler ◽  
...  
Keyword(s):  
Design Space ◽  
Potent Inhibitor ◽  
Glycogen Synthase ◽  
Selective Inhibition ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3 ◽  
Cellular Functions ◽  
Starting Point ◽  
Potential Therapeutics

Glycogen synthase kinase-3 (GSK-3) is a multitasking protein kinase that regulates numerous critical cellular functions. Not surprisingly, elevated GSK-3 activity has been implicated in a host of diseases including pathological inflammation, diabetes, cancer, arthritis, asthma, bipolar disorder, and Alzheimer’s. Therefore, reagents that inhibit GSK-3 activity provide a means to investigate the role of GSK-3 in cellular physiology and pathophysiology and could become valuable therapeutics. Finding a potent inhibitor of GSK-3 that can selectively target this kinase, among over 500 protein kinases in the human genome, is a significant challenge. Thus there remains a critical need for the identification of selective inhibitors of GSK-3. In this work, we introduce a novel small organic compound, namely COB-187, which exhibits potent and highly selective inhibition of GSK-3. Specifically, this study 1) utilized a molecular screen of 414 kinase assays, representing 404 unique kinases, to reveal that COB-187 is a highly potent and selective inhibitor of GSK-3; 2) utilized a cellular assay to reveal that COB-187 decreases the phosphorylation of canonical GSK-3 substrates indicating that COB-187 inhibits cellular GSK-3 activity; and 3) reveals that a close isomer of COB-187 is also a selective and potent inhibitor of GSK-3. Taken together, these results demonstrate that we have discovered a region of chemical design space that contains novel GSK-3 inhibitors. These inhibitors will help to elucidate the intricate function of GSK-3 and can serve as a starting point for the development of potential therapeutics for diseases that involve aberrant GSK-3 activity.

scholarly journals Role of glycogen synthase kinase-3β inhibitor AZD1080 in ovarian cancer

2016 ◽  
pp. 1225
Author(s):  
Yang Zhao ◽  
Shuo Chen ◽  
Kai-Xuan Sun ◽  
Miao-Xiao Feng ◽  
Bo-Liang Liu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Glycogen Synthase ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3
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