P3-315: The role of glycogen synthase kinase -3β (GSK-3β) and cyclin-dependent kinase-5 (CDK5) in the generation of hyperphosphorylated tau relevant to Alzheimer's disease

2006 ◽  
Vol 2 ◽  
pp. S467-S468
Author(s):  
Anjan Seereeram ◽  
Malcolm Saxton ◽  
Malcolm A. Ward ◽  
Brian H. Anderton ◽  
Diane P. Hanger
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glycogen Synthase ◽  
Glycogen Synthase Kinase ◽  
Hyperphosphorylated Tau ◽  
Cyclin Dependent Kinase ◽  
Glycogen Synthase Kinase 3Β ◽  
Gsk 3Β ◽  
Cyclin Dependent Kinase 5

scholarly journals Targeting Glycogen Synthase Kinase-3βfor Therapeutic Benefit against Oxidative Stress in Alzheimer's Disease: Involvement of the Nrf2-ARE Pathway

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Katja Kanninen ◽  
Anthony R. White ◽  
Jari Koistinaho ◽  
Tarja Malm
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glycogen Synthase ◽  
Glycogen Synthase Kinase ◽  
Therapeutic Effects ◽  
Related Factor ◽  
Nrf2 Pathway ◽  
Gsk 3Β

Specific regions of the Alzheimer's disease (AD) brain are burdened with extracellular protein deposits, the accumulation of which is concomitant with a complex cascade of overlapping events. Many of these pathological processes produce oxidative stress. Under normal conditions, oxidative stress leads to the activation of defensive gene expression that promotes cell survival. At the forefront of defence is the nuclear factor erythroid 2-related factor 2 (Nrf2), a transcription factor that regulates a broad spectrum of protective genes. Glycogen synthase kinase-3β (GSK-3β) regulates Nrf2, thus making this kinase a potential target for therapeutic intervention aiming to boost the protective activation of Nrf2. This paper aims to review the neuroprotective role of Nrf2 in AD, with special emphasis on the role of GSK-3β in the regulation of the Nrf2 pathway. We also examine the potential of inducing GSK-3β by small-molecule activators, dithiocarbamates, which potentially exert their beneficial therapeutic effects via the activation of the Nrf2 pathway.

scholarly journals Presenilin 1 associates with glycogen synthase kinase-3β and its substrate tau

1998 ◽  
Vol 95 (16) ◽  
pp. 9637-9641 ◽  
Author(s):  
Akihiko Takashima ◽  
Miyuki Murayama ◽  
Ohoshi Murayama ◽  
Toshiyuki Kohno ◽  
Toshiyuki Honda ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glycogen Synthase ◽  
Amyloid Β ◽  
Glycogen Synthase Kinase ◽  
Presenilin 1 ◽  
Amyloid Β Protein ◽  
Glycogen Synthase Kinase 3Β ◽  
Β Protein ◽  
Gsk 3Β

Families bearing mutations in the presenilin 1 (PS1) gene develop Alzheimer’s disease. Previous studies have shown that the Alzheimer-associated mutations in PS1 increase production of amyloid β protein (Aβ1–42). We now show that PS1 also regulates phosphorylation of the microtubule-associated protein tau. PS1 directly binds tau and a tau kinase, glycogen synthase kinase 3β (GSK-3β). Deletion studies show that both tau and GSK-3β bind to the same region of PS1, residues 250–298, whereas the binding domain on tau is the microtubule-binding repeat region. The ability of PS1 to bring tau and GSK-3β into close proximity suggests that PS1 may regulate the interaction of tau with GSK-3β. Mutations in PS1 that cause Alzheimer’s disease increase the ability of PS1 to bind GSK-3β and, correspondingly, increase its tau-directed kinase activity. We propose that the increased association of GSK-3β with mutant PS1 leads to increased phosphorylation of tau.

Alzheimer Disease and Related Tauopathies: Possible Neuroprotective Strategies

2018 ◽  
Vol 2 (3) ◽  
pp. 01-02
Author(s):  
Meketa Muñoz
Keyword(s):  
Alzheimer Disease ◽  
Glycogen Synthase ◽  
Vital Role ◽  
Current Therapy ◽  
Cyclin Dependent Kinase ◽  
Abnormal Hyperphosphorylation ◽  
Neuroprotective Strategies ◽  
Gsk 3Β ◽  
Cyclin Dependent Kinase 5

Alzheimer disease (AD) is the most common cause of dementia in adults. The current therapy for AD has only moderate efficacy in controlling symptoms, and it does not cure the disease. Recent studies have suggested that abnormal hyperphosphorylation of tau in the brain plays a vital role in the molecular pathogenesis of AD and in neurodegeneration. This article reviews the current advances in understanding of tau protein, regulation of tau phosphorylation, and the role of its abnormal hyperphosphorylation in neurofibrillary degeneration. Furthermore, several therapeutic strategies for treating AD on the basis of the important role of tau hyperphosphorylation in the pathogenesis of the disease are described. These strategies include (1) inhibition of glycogen synthase kinase-3β (GSK-3β), cyclin-dependent kinase 5 (cdk5), and other tau kinases; (2) restoration of PP2A activity; and (3) targeting tau O-GlcNAcylation. Development of drugs on the basis of these strategies is likely to lead to disease-modifying therapies for AD.

Glycogen synthase kinase-3β and tau genes interact in Alzheimer's disease

2008 ◽  
Vol 64 (4) ◽  
pp. 446-454 ◽  
Author(s):  
John B. J. Kwok ◽  
Clement T. Loy ◽  
Gillian Hamilton ◽  
Edmond Lau ◽  
Marianne Hallupp ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glycogen Synthase ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3Β
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