scholarly journals Glycogen Synthase Kinase-3β: A Mediator of Inflammation in Alzheimer's Disease?

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Jari Koistinaho ◽  
Tarja Malm ◽  
Gundars Goldsteins
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glycogen Synthase ◽  
Immune Defense ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3 ◽  
Normal Brain ◽  
Brain Functions ◽  
The Brain

Proliferation and activation of microglial cells is a neuropathological characteristic of brain injury and neurodegeneration, including Alzheimer's disease. Microglia act as the first and main form of immune defense in the nervous system. While the primary function of microglia is to survey and maintain the cellular environment optimal for neurons in the brain parenchyma by actively scavenging the brain for damaged brain cells and foreign proteins or particles, sustained activation of microglia may result in high production of proinflammatory mediators that disturb normal brain functions and even cause neuronal injury. Glycogen synthase kinase-3βhas been recently identified as a major regulator of immune system and mediates inflammatory responses in microglia. Glycogen synthase kinase-3βhas been extensively investigated in connection to tau and amyloidβtoxicity, whereas reports on the role of this enzyme in neuroinflammation in Alzheimer's disease are negligible. Here we review and discuss the role of glycogen synthase-3βin immune cells in the context of Alzheimer's disease pathology.

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 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.

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