scholarly journals Regulation of Cell Survival Mechanisms in Alzheimer's Disease by Glycogen Synthase Kinase-3

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Marjelo A. Mines ◽  
Eleonore Beurel ◽  
Richard S. Jope
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glycogen Synthase ◽  
Apoptotic Cell ◽  
Amyloid Β ◽  
Neuronal Loss ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3 ◽  
Amyloid Β Peptide ◽  
Apoptotic Signaling

A pivotal role has emerged for glycogen synthase kinase-3 (GSK3) as an important contributor to Alzheimer's disease pathology. Evidence for the involvement of GSK3 in Alzheimer's disease pathology and neuronal loss comes from studies of GSK3 overexpression, GSK3 localization studies, multiple relationships between GSK3 and amyloid β-peptide (Aβ), interactions between GSK3 and the microtubule-associated tau protein, and GSK3-mediated apoptotic cell death. Apoptotic signaling proceeds by either an intrinsic pathway or an extrinsic pathway. GSK3 is well established to promote intrinsic apoptotic signaling induced by many insults, several of which may contribute to neuronal loss in Alzheimer's disease. Particularly important is evidence that GSK3 promotes intrinsic apoptotic signaling induced by Aβ. GSK3 appears to promote intrinsic apoptotic signaling by modulating proteins in the apoptosis signaling pathway and by modulating transcription factors that regulate the expression of proteins involved in apoptosis. Thus, GSK3 appears to contribute to several neuropathological mechanisms in Alzheimer's disease, including apoptosis-mediated neuronal loss.

The active form of glycogen synthase kinase-3? is associated with granulovacuolar degeneration in neurons in Alzheimer's disease

2002 ◽  
Vol 103 (2) ◽  
pp. 91-99 ◽  
Author(s):  
Allal Boutajangout ◽  
Karelle Leroy ◽  
Authelet M. ◽  
Brian Anderton ◽  
Jean-Pierre Brion ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glycogen Synthase ◽  
Active Form ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3 ◽  
Granulovacuolar Degeneration

Mechanism of Glycogen Synthase Kinase-3β alterations by Alzheimer’s disease amyloid β peptides

2011 ◽  
Vol 63 (5) ◽  
pp. 1296
Author(s):  
Martyna Songin ◽  
Magdalena Cieślik ◽  
Magdalena Gąssowska ◽  
Grzegorz A. Czapski ◽  
Joanna B. Strosznajder
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glycogen Synthase ◽  
Amyloid Β ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3Β

scholarly journals Programmed Cell Death Protein 1 Blockade Reduces Glycogen Synthase Kinase 3β Activity and Tau Hyperphosphorylation in Alzheimer’s Disease Mouse Models

2021 ◽  
Vol 9 ◽  
Author(s):  
Yulian Zou ◽  
Chen-Ling Gan ◽  
Zhiming Xin ◽  
Hai-Tao Zhang ◽  
Qi Zhang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Mouse Models ◽  
Glycogen Synthase ◽  
Neuronal Damage ◽  
Amyloid Β ◽  
Glycogen Synthase Kinase ◽  
Tau Hyperphosphorylation

Alzheimer’s disease (AD) is a central nervous system degenerative disease, with no effective treatment to date. Administration of immune checkpoint inhibitors significantly reduces neuronal damage and tau hyperphosphorylation in AD, but the specific mechanism is unclear. Here, we found that programmed cell death-receptor 1 (PD1) and its ligand PDL1 were induced by an intracerebroventricular injection of amyloid-β; they were significantly upregulated in the brains of APP/PS1, 5×FAD mice and in SH-SY5Y-APP cell line compared with control. The PD1 and PDL1 levels positively correlated with the glycogen synthase kinase 3 beta (GSK3β) activity in various AD mouse models, and the PDL1-GSK3β immune complex was found in the brain. The application of PD1-blocking antibody reduced tau hyperphosphorylation and GSK3β activity and prevented memory impairments. Mechanistically, we identified PD1 as a critical regulator of GSK3β activity. These results suggest that the immune regulation of the PD1/PDL1 axis is closely involved in AD.

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.

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