p(MGI:Gsk3b)

Entity

Name

Gsk3b

Namespace

MGI

Namespace Version

20170725

Namespace URL

https://arty.scai.fraunhofer.de/artifactory/bel/namespace/mgi-mouse-genes/mgi-mouse-genes-20170725.belns

The authors argue that the effects of rosiglitazone were due to the activation of the wnt signaling cascade which they show by an increase in b-catenin expression and a decrease in GSK-3b levels [63]. PubMed:21718217

Recently, a novel group of M1 partial agonists was developed (AF102B, AF150(S) and AF267B-i) [129]. In a series of studies using the 3x transgenic-AD mice, which recapitulate the major pathologies of AD [130], chronic AF267B treatment rescued cognitive impairment and decreased Abeta42 and tau pathologies in the cortex and hippocampus. These changes were associated with M1 mAChR-mediated activation of the TNFalpha-converting enzyme ADAM17/TACE, decreased BACE1 steady state levels and inhibition of GSK3beta [130]. PubMed:18986241

Taken all together, we think that activation of GSK-3b and p38 should be responsible for MG-induced tau hyperphosphorylation. PubMed:22798221

ATRA prevents the accumulation of amyloid plaques and APP processing into Ab through downregulation of Cdk5 in APP/PS1 mice. These results suggested that the administration of ATRA inhibited activity of Cdk5 and GSK3b and attenuated the formation of p-tau aggregation, including p-CRMP2 and p-WAVE1 in the 33Tg mouse brain. PubMed:26400044

Here we report the discovery of a new first-in-class small-molecule (CM-414) that acts as a dual inhibitor of PDE5 and HDACs. We have used this compound as a chemical probe to validate this systems therapeutics strategy, where an increase in the activation of cAMP/cGMP-responsive element-binding protein (CREB) induced by PDE5 inhibition, combined with moderate HDAC class I inhibition, leads to efficient histone acetylation. This molecule rescued the impaired long-term potentiation evident in hippocampal slices from APP/PS1 mice. Chronic treatment of Tg2576 mice with CM-414 diminished brain Aβ and tau phosphorylation (pTau) levels, increased the inactive form of GSK3β, reverted the decrease in dendritic spine density on hippocampal neurons, and reversed their cognitive deficits, at least in part by inducing the expression of genes related to synaptic transmission. PubMed:27550730

The levels of CDK5, its regulatory subunits (p35 and p25) and calpain (including calpain1 and calpain2), but not GSK3ß, were significantly increased in E4FAD mice compared to E3FAD mice. PubMed:27087442

In this study, we demonstrated that GLP-1RA could inhibit oxidative stress and repair mitochondrial damage in addition to decreasing tau hyperphosphorylation in PC12 cells treated with AGEs. Importantly, we first observed AGEs in the circulatory system could induce tau hyperphosphorylation after we injected AGEs (1μg/kg bodyweight) into the mice tail vein. We found GLP-1RA could promote mitochondrial biogenesis and antioxidant system via regulating peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) signaling pathway in vivo besides down-regulating the activity of glycogen synthase kinase 3β (GSK-3β) to reverse tau hyperphosphorylation directly. PubMed:25987199

We studied underlying pathomechanisms in tauopathies using pR5 mice that express the P301L tau mutation found in familial forms of frontotemporal dementia. In a longitudinal study we investigated the functional status of glycogen synthase kinase-3 and correlated it with the appearance of distinct tau phospho-epitopes. Neurons displaying increases in activating phosphorylation of glycogen synthase kinase-3α/β at tyrosine 279/216 also showed an intense rather than moderate AT8 (phospho-Ser202/Thr205 tau) immunoreactivity, and immunoreactivity for AT100 (phospho-Ser212/Thr214 tau) and phosphorylated Ser422, phospho-epitopes associated with fibrillar tau pathology. PubMed:23294633

We studied underlying pathomechanisms in tauopathies using pR5 mice that express the P301L tau mutation found in familial forms of frontotemporal dementia. In a longitudinal study we investigated the functional status of glycogen synthase kinase-3 and correlated it with the appearance of distinct tau phospho-epitopes. Neurons displaying increases in activating phosphorylation of glycogen synthase kinase-3α/β at tyrosine 279/216 also showed an intense rather than moderate AT8 (phospho-Ser202/Thr205 tau) immunoreactivity, and immunoreactivity for AT100 (phospho-Ser212/Thr214 tau) and phosphorylated Ser422, phospho-epitopes associated with fibrillar tau pathology. PubMed:23294633

Taken all together, we think that activation of GSK-3b and p38 should be responsible for MG-induced tau hyperphosphorylation. PubMed:22798221

Taken all together, we think that activation of GSK-3b and p38 should be responsible for MG-induced tau hyperphosphorylation. PubMed:22798221

Taken all together, we think that activation of GSK-3b and p38 should be responsible for MG-induced tau hyperphosphorylation. PubMed:22798221

Taken all together, we think that activation of GSK-3b and p38 should be responsible for MG-induced tau hyperphosphorylation. PubMed:22798221

Taken all together, we think that activation of GSK-3b and p38 should be responsible for MG-induced tau hyperphosphorylation. PubMed:22798221

Taken all together, we think that activation of GSK-3b and p38 should be responsible for MG-induced tau hyperphosphorylation. PubMed:22798221

Taken all together, we think that activation of GSK-3b and p38 should be responsible for MG-induced tau hyperphosphorylation. PubMed:22798221