scholarly journals GSK-3 in Neurodegenerative Diseases

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Peng Lei ◽  
Scott Ayton ◽  
Ashley I. Bush ◽  
Paul A. Adlard
Keyword(s):  
Cell Culture ◽  
Neurodegenerative Diseases ◽  
Glycogen Synthase ◽  
Transgenic Animal ◽  
Tau Phosphorylation ◽  
Glycogen Synthase Kinase 3 ◽  
Cellular Processes ◽  
Amyloid A ◽  
Transgenic Animal Models

Glycogen synthase kinase-3 (GSK-3) regulates multiple cellular processes, and its dysregulation is implicated in the pathogenesis of diverse diseases. In this paper we will focus on the dysfunction of GSK-3 in Alzheimer’s disease and Parkinson’s disease. Specifically, GSK-3 is known to interact with tau,β-amyloid (Aβ), andα-synuclein, and as such may be crucially involved in both diseases. Aβproduction, for example, is regulated by GSK-3, and its toxicity is mediated by GSK-induced tau phosphorylation and degeneration.α-synuclein is a substrate for GSK-3 and GSK-3 inhibition protects against Parkinsonian toxins. Lithium, a GSK-3 inhibitor, has also been shown to affect tau, Aβ, andα-synuclein in cell culture, and transgenic animal models. Thus, understanding the role of GSK-3 in neurodegenerative diseases will enhance our understanding of the basic mechanisms underlying the pathogenesis of these disorders and also facilitate the identification of new therapeutic avenues.

scholarly journals Unravelling the Role of Glycogen Synthase Kinase-3 in Alzheimer’s Disease-Related Epileptic Seizures

2020 ◽  
Vol 21 (10) ◽  
pp. 3676 ◽  
Author(s):  
Runxuan Lin ◽  
Nigel Charles Jones ◽  
Patrick Kwan
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glycogen Synthase ◽  
Epileptic Seizures ◽  
Transgenic Animal ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3 ◽  
Key Factor ◽  
Transgenic Animal Models

Alzheimer’s disease (AD) is the most common form of dementia. An increasing body of evidence describes an elevated incidence of epilepsy in patients with AD, and many transgenic animal models of AD also exhibit seizures and susceptibility to epilepsy. However, the biological mechanisms that underlie the occurrence of seizure or increased susceptibility to seizures in AD is unknown. Glycogen synthase kinase-3 (GSK-3) is a serine/threonine kinase that regulates various cellular signaling pathways, and plays a crucial role in the pathogenesis of AD. It has been suggested that GSK-3 might be a key factor that drives epileptogenesis in AD by interacting with the pathological hallmarks of AD, amyloid precursor protein (APP) and tau. Furthermore, seizures may also contribute to the progression of AD through GSK-3. In this way, GSK-3 might be involved in initiating a vicious cycle between AD and seizures. This review aims to summarise the possible role of GSK-3 in the link between AD and seizures. Understanding the role of GSK-3 in AD-associated seizures and epilepsy may help researchers develop new therapeutic approach that can manage seizure and epilepsy in AD patients as well as decelerate the progression of AD.

scholarly journals The role of glycogen synthase kinase 3 (GSK3) in cancer with emphasis on ovarian cancer development and progression: A comprehensive review

2020 ◽  
Author(s):  
Mislav Glibo ◽  
Alan Serman ◽  
Valentina Karin-Kujundzic ◽  
Ivanka Bekavac Vlatkovic ◽  
Berivoj Miskovic ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Glycogen Synthase ◽  
Alpha Helix ◽  
Glycogen Synthase Kinase ◽  
Cancer Development ◽  
Glycogen Synthase Kinase 3 ◽  
Serine Threonine Kinase ◽  
Therapeutic Implications ◽  
Cellular Processes

Glycogen synthase kinase 3 (GSK3) is a monomeric serine-threonine kinase discovered in 1980 in a rat skeletal muscle. It has been involved in various cellular processes including embryogenesis, immune response, inflammation, apoptosis, autophagy, wound healing, neurodegeneration and carcinogenesis. GSK3 exists in two different isoforms, GSK3α and GSK3β, both containing seven antiparallel beta-plates, a short linking part and an alpha helix, but coded by different genes and variously expressed in human tissues. In the current review, we comprehensively appraise the current literature on the role of GSK3 in various cancers with emphasis on ovarian carcinoma. Our findings indicate that the role of GSK3 in ovarian cancer development cannot be decisively determined as the currently available data support both prooncogenic and tumor-suppressive effects. Likewise, the clinical impact of GSK3 expression on ovarian cancer patients and its potential therapeutic implications are also limited. Further studies are needed to fully elucidate the pathophysiological and clinical implications of GSK3 activity in ovarian cancer.

Glycogen Synthase Kinase 3 (GSK3): Its Role and Inhibitors

2020 ◽  
Vol 20 (17) ◽  
pp. 1522-1534 ◽  
Author(s):  
Pankaj Wadhwa ◽  
Priti Jain ◽  
Hemant R. Jadhav
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glycogen Synthase ◽  
High Specificity ◽  
Tau Phosphorylation ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3 ◽  
Important Target ◽  
The Brain

: Glycogen Synthase Kinase 3 (GSK3) is one of the Serine/Threonine protein kinases, which has gained a lot of attention for its role in a variety of pathways. It has two isoforms, GSK3α and GSK3β. However, GSK3β is highly expressed in different areas of the brain and has been implicated in Alzheimer’s disease as it is involved in tau phosphorylation. Due to its high specificity concerning substrate recognition, GSK3 has been considered as an important target. In the last decade, several GSK3 inhibitors have been reported and two molecules are in clinical trials. This review collates the information published in the last decade about the role of GSK3 in Alzheimer’s disease and progress in the development of its inhibitors. Using this collated information, medicinal chemists can strategize and design novel GSK3 inhibitors that could be useful in the treatment of Alzheimer’s disease.

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.

The Regulatory Perspective on the Role of Toxicology in Protecting the Public Health

1999 ◽  
Vol 18 (3) ◽  
pp. 209-212 ◽  
Author(s):  
Sidney Green
Keyword(s):  
Public Health ◽  
Adverse Effects ◽  
Transgenic Animal ◽  
Regulatory Agencies ◽  
Basic Information ◽  
The Public ◽  
Regulatory Perspective ◽  
Transgenic Animal Models ◽  
New Guidelines

The role of toxicology as far as regulatory agencies are concerned is to assist in determining the safety of products/substances to which humans and wildlife are exposed. This is accomplished primarily by assessing the adverse effects of these products/substances. In a number of cases, the benefits of the product/substance are balanced against the adverse effects or hazards. Often the stimulus for new guidelines, policies, and regulations is the discovery of a heretofore unknown hazard, or the presumption that a hazard exists for which current methodologies are deemed insufficient or totally lacking. An example of the latter type of stimulus are the so-called, endocrine modulators or disruptors. Research in toxicology also serves as a stimulus for new guidelines, policies and regulations, for example, dietary restriction and transgenic animal models. There is a painstaking process associated with the development of policy by regulatory agencies regardless of which stimulus operates. This process, however, does not meet with success in all instances. One of the major difficulties in establishing new guidelines, policies, and regulations, is that of bringing about a balance between risk and safety. The role of toxicology in providing basic information which is then used to make decisions and bring about this balance is pivotal. Toxicology can be the stimulus for new guidelines, policies, and regulations, i.e., contribute early in the process or it can contribute at a later stage in providing information to substantiate or refute the need for new guidelines, policies, or regulations.

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