A pan-cortical brain region co-expression network analysis identified pathways and genes (eg, glycogen synthase kinase 3β) that were significantly associated with clinical characteristics of AD (such as neurofibrillary score) in males only.
Following a multitarget approach, in this paper a series of polycyclic maleimide-based derivatives were designed and synthesized aimed at simultaneously modulate neuronal calcium channels and glycogen synthase kinase 3-beta (GSK-3β), validated targets to combat Alzheimer' disease.
Glycogen synthase kinase-3β (GSK-3β) represents a relevant drug target for the treatment of neurodegenerative pathologies including Alzheimer's disease.
Evidence indicates that Schisandrin inhibition of Aβ<sub>1-42</sub> -mediated cellular damage in AD neurons may involve activation of the PI3K/Akt signaling pathway where up-regulation of <i>p</i>-Akt activity consequently leads downstream to decreased activity of <i>p</i>-GSK-3β phosphorylation accompanied by reduced tau protein.
Glycogen synthase kinase 3β (GSK3β) is a key component of pathogenesis in Alzheimer's disease, and its inhibitors can restore cognitive function as therapeutic interventions in neurodegenerative diseases.
It is concluded that the analogues to GSK-3β inhibitors were optimized in relation to the toxicity of template, being presented as promising drug candidates for Alzheimer's disease treatment.
For this reason, other biochemical pathways associated with the pathophysiology of AD have been explored as alternatives to the treatment of this condition such as inhibition of β-secretase and glycogen synthase kinase-3β.
In AD, GSK-3β plays an important role in hyperphosphorylation of microtubule-associated protein tau (tau), which is one of the pathological features in AD.
Tau-Centric Multitarget Approach for Alzheimer's Disease: Development of First-in-Class Dual Glycogen Synthase Kinase 3β and Tau-Aggregation Inhibitors.
Glycogen synthase kinase 3β (GSK3β) is a highly conserved serine/threonine kinase that has been implicated in both psychiatric and neurodegenerative diseases including schizophrenia, bipolar disorder, and Alzheimer's disease; therefore regulating its activity has become an important strategy for treatment of cognitive impairments in these disorders.
Therefore, one of the mechanisms of action of KK against AD may be the inhibition of GSK-3β and one of the active components of KK is the root of <i>S. miltiorrhiza</i> and its constituents: rosmarinic acid, magnesium lithospermate B, and salvianolic acids A, B, and C. Our results demonstrate the pharmacological basis for the use of KK against AD.
Melatonin significantly ameliorated the cognitive function and mitochondrial damage in AD mice, reduced the expression levels of GSK-3β, caspase-3, Aβ<sub>1-42</sub> , BACE1, p-tau protein and increased the expressions of PP2A and Bcl-2.
Consistent with its critical roles in normal cells, abnormalities in GSK-3β activity have been implicated in diabetes, heart disease, Parkinson disease, and Alzheimer's disease.
Previous studies in high-fat diet-induced AD animal models have shown that brain insulin resistance in these animals leads to the accumulation of amyloid beta (Aβ) and the reduction in GSK-3β phosphorylation, which promotes tau phosphorylation to cause AD.
A physicochemical descriptor based method for effective and rapid screening of dual inhibitors against BACE-1 and GSK-3β as targets for Alzheimer's disease.
Thus, our previous and present findings raise the unifying prospect that Aβ•CaSR signaling plays a crucial role in AD development and progression by simultaneously activating (i) the amyloidogenic processing of amyloid precursor holoprotein, whose upshot is a surplus production and secretion of Aβ<sub>42</sub> oligomers, and (ii) the GSK-3β-mediated increased production of p-Tau oligomers which are next released extracellularly inside exosomes.
Accumulative evidence demonstrates that GSK-3β inactivation may be potentially developed as the promising strategy in management of many diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD).
7-bromoindirubin-3-oxime (7Bio), an indirubin derivative derived from indirubin-3-oxime, possesses inhibitory effects against cyclin-dependent kinase-5 (CDK5) and glycogen synthase kinase-3β (GSK3β), two pharmacological targets of Alzheimer's disease (AD).
Glycogen synthase kinase 3β (GSK-3β) is a widely investigated molecular target for numerous diseases including Alzheimer's disease, cancer, and diabetes mellitus.
Data presented hereby will display a plethora of information as to how to interfere with progression of AD through the route of GSK-3β activity control.