|
Alzheimer's Disease
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Malathion exposure induced spatial learning and memory deficits with a simultaneous decrease of PSD93 and TAU hyperphosphorylation at multiple AD-related phosphorylation sites with activation of glycogen synthase kinase-3β (GSK-3β) and inhibition of protein phosphatase-2A (PP2A).
|
30789100 |
2020 |
|
Alzheimer's Disease
|
0.100 |
Biomarker
|
disease |
BEFREE |
The administration of okadaic acid (OKA), a potent PP2A and PP1 inhibitor, is a common research tool for inducing AD-like alterations such as tau hyperphosphorylation and cognitive decline.
|
30586637 |
2019 |
|
Alzheimer's Disease
|
0.100 |
Biomarker
|
disease |
BEFREE |
Based on these findings, we speculate that AD P-tau seeds hyperphosphorylated tau to form aggregates, which resist to the dephosphorylation by PP2A, resulting in hyperphosphorylation and pathology of tau.
|
30890929 |
2019 |
|
Alzheimer's Disease
|
0.100 |
Biomarker
|
disease |
BEFREE |
That is Aβ-PirB-PP2A-GSK3β-MACF1 axis might give rise to AD.
|
31383338 |
2019 |
|
Alzheimer's Disease
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Results showed that co-administration of CA to d-gal/AlCl<sub>3</sub> induced AD-like rat models significantly increased the levels of protein phosphatase 2 (PP2A) and decreased the levels of glycogen synthase kinase-3 beta (GSK-3β).
|
31014012 |
2019 |
|
Alzheimer's Disease
|
0.100 |
Biomarker
|
disease |
BEFREE |
However, the lead compound of this family (5f) presented an activating profile of the phosphatase 2A (PP2A) and showed interesting outcomes in experimental in vivo models of AD and stroke.
|
30739821 |
2019 |
|
Alzheimer's Disease
|
0.100 |
Biomarker
|
disease |
BEFREE |
Okadaic acid (OKA), a potent inhibitor of PP1 and PP2A, reportedly leads to cognitive decline and Alzheimer's disease (AD)-like pathology.
|
30630043 |
2019 |
|
Alzheimer's Disease
|
0.100 |
Biomarker
|
disease |
BEFREE |
Most of the compounds mitigated the okadaic acid-provoked inhibition of PP2A and protected SH-SY5Y cells against toxic stimuli related to Tau-hyperphosphorylation and oxidative stress, similarly to the observed in Alzheimer's disease (AD).
|
30099252 |
2018 |
|
Alzheimer's Disease
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Results reveal that SMC 1) reduces oxidative stress and neuro-inflammation; 2) modulates the distribution and levels of several metal ions; 3) decreases amyloid-β peptide (Aβ) generation by inhibiting the expression of its precursor protein APP and β-secretase (BACE1); and 4) attenuates tau hyperphosphorylation and neurofibrillary tangles (NFT) formation via promoting protein phosphatase 2A (PP2A) activity, thereby preserving synaptic proteins and neuron activities and finally improving spatial learning and memory deficits in AD model mice.
|
29688618 |
2018 |
|
Alzheimer's Disease
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
In summary, we show that CIP2A overexpression causes PP2A inhibition and AD-related cellular pathology and cognitive deficits, pointing to CIP2A as a potential target for AD therapy.
|
30021167 |
2018 |
|
Alzheimer's Disease
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Microcystin-leucine-arginine (MC-LR) has been implicated as a potential environmental factor in Alzheimer's disease because of its potent inhibition of protein phosphatase 2A (PP2A) activity, but experimental evidence to support its detailed neurotoxic effects and their underlying mechanisms has been lacking.
|
29228318 |
2018 |
|
Alzheimer's Disease
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Together, our data suggest that CPPs might prevent AD-like tau hyperphosphorylation via activation of PP2A and attenuates AD-like cognitive impairments through restoring the synaptic plasticity and synaptogenesis.
|
30542264 |
2018 |
|
Alzheimer's Disease
|
0.100 |
Biomarker
|
disease |
BEFREE |
Similarly, Western blot analyses showed a decrease of methyl-PP2A and an increase of demethyl-PP2A with a concomitant reduction in the methyl/demethyl PP2A ratio in both PSP (74%) and AD (76%) brains.
|
29281045 |
2018 |
|
Alzheimer's Disease
|
0.100 |
Biomarker
|
disease |
BEFREE |
Substituent effect of N-benzylated gramine derivatives that prevent the PP2A inhibition and dissipate the neuronal Ca<sup>2+</sup> overload, as a multitarget strategy for the treatment of Alzheimer's disease.
|
29656989 |
2018 |
|
Alzheimer's Disease
|
0.100 |
Biomarker
|
disease |
BEFREE |
These findings suggest that targeting the tau phosphatase PP2A has therapeutic potential for preventing memory impairments and reducing the tau pathology seen in AD and other tauopathies.
|
29920069 |
2018 |
|
Alzheimer's Disease
|
0.100 |
Biomarker
|
disease |
BEFREE |
The overexpression of endogenous protein inhibitors of PP2A, SET and CIP2A, is tightly linked to the progression of various human cancers, as well as Alzheimer's disease.
|
30341686 |
2018 |
|
Alzheimer's Disease
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
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.
|
28994117 |
2018 |
|
Alzheimer's Disease
|
0.100 |
Biomarker
|
disease |
BEFREE |
Our findings shed new light on the role of calpain-GSK-3β-PP2A in tau pathogenesis of AD.
|
28267204 |
2017 |
|
Alzheimer's Disease
|
0.100 |
Biomarker
|
disease |
BEFREE |
Several abnormalities of PP2A have been reported in AD, including among others decreased protein levels of PP2A, decreased mRNA and protein levels of the catalytic subunit PP2A<sub>C</sub> and variable regulatory B subunits and reduced methylation of the catalytic subunit, all of which results in disruption of the PP2A phosphatase activity.
|
28720530 |
2017 |
|
Alzheimer's Disease
|
0.100 |
Biomarker
|
disease |
BEFREE |
The most important phosphatase that is capable of dephosphorylating Tau at AD specific phospho-sites is protein phosphatase 2 A (PP2A).
|
29062069 |
2017 |
|
Alzheimer's Disease
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Activation of PP2A by sodium selenate could increase active β-catenin level and inhibit GSK3β activity in the hippocampal tissue and primarily cultured neurons of AD model mouse, leading to activation of Wnt/β-catenin signaling and transactivation of target genes, including positively-regulated genes c-myc, survivin, TXNRD2 and negatively-regulated gene BACE1.
|
28711506 |
2017 |
|
Alzheimer's Disease
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Collectively, these results suggest that the loss of cerebrovascular homeostasis that occurs in AD might be a downstream event of the compromised activity and/or expression of PP2A, which is observed in the brain of individuals affected with this devastating neurodegenerative disorder.
|
26732598 |
2017 |
|
Alzheimer's Disease
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
These data add to the accumulating evidence suggesting that interventions with pharmacological agents, such as EHT, that target PP2A activity may be therapeutically beneficial for AD and other neurological conditions.
|
29253878 |
2017 |
|
Alzheimer's Disease
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Oxygen deprivation (OD) resulted in tau dephosphorylation at several AD-related residues and activation of GSK3β and phosphatase PP2A.
|
28869464 |
2017 |
|
Alzheimer's Disease
|
0.100 |
Biomarker
|
disease |
BEFREE |
Deficits in protein phosphatase 2A (PP2A) are associated with tau hyperphosphorylation in AD.
|
26836014 |
2016 |