|
Alzheimer's Disease
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Taken together, our data showed that AMPK activation inhibits p-tau396 expression in a GSK3β- and PP2A-dependent manner, and suggest that differential regulation of tau phosphorylation in young SAMP8 mice by AMPK plays a compensatory role against accelerated senescence in this AD animal model.
|
25737046 |
2015 |
|
Alzheimer's Disease
|
0.100 |
Biomarker
|
disease |
BEFREE |
These findings suggest a previously undiscovered etiopathogenic relationship between sporadic forms of AD and ALS that is linked to I2(PP2A) and the potential of I2(PP2A)-based therapeutics for these diseases.
|
24136402 |
2014 |
|
Alzheimer's Disease
|
0.100 |
Biomarker
|
disease |
BEFREE |
The current study further presents an inducible cell model (Tet-Off system) of AD-type abnormal hyperphosphorylation of Tau by expressing I2 (PP2A) in which the NLS was inactivated by (179)RKR(181) → AAA along with (168)KR(169) → AA mutations.
|
25128526 |
2014 |
|
Alzheimer's Disease
|
0.100 |
Biomarker
|
disease |
BEFREE |
Phosphotyrosyl phosphatase activator (PTPA) is decreased in the brains of Alzheimer's disease (AD) and AD transgenic mouse models.
|
24821282 |
2014 |
|
Alzheimer's Disease
|
0.100 |
Biomarker
|
disease |
BEFREE |
Therefore, in vivo silencing I2(PP2A) may rescue PP2A and mitigate AD neurodegeneration.
|
23922015 |
2013 |
|
Alzheimer's Disease
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
In conclusion, the current study has identified a novel mechanism that causes cytoplasmic detention of SET with a new NLS-dependent CKII-associated phosphorylation of Ser9, suggesting that inhibition of CKII arrests cytoplasmic accumulation of SET and thus preserves PP2A activity in AD brains.
|
23374587 |
2013 |
|
Alzheimer's Disease
|
0.100 |
PosttranslationalModification
|
disease |
BEFREE |
We have reported that altered leucine carboxyl methyltransferase (LCMT1)-dependent PP2A methylation is associated with down-regulation of PP2A holoenzymes containing the Bα subunit (PP2A/Bα) and subsequent accumulation of phosphorylated Tau in N2a cells, in vivo and in AD.
|
23943618 |
2013 |
|
Alzheimer's Disease
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Protein phosphatase-2A (PP2A) activity is significantly suppressed in Alzheimer's disease.
|
22732552 |
2012 |
|
Alzheimer's Disease
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Rs7768046 in the FYN kinase gene and rs913275 in the PPP2R4 phosphatase gene were both associated with CSF p-tau and t-tau levels in AD.
|
22927204 |
2012 |
|
Alzheimer's Disease
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Because the impacts of tau phosphorylation on its biological activity and on neurofibrillary degeneration are site-specific, this study provides a new insight into the role of PP2A down-regulation in neurofibrillary degeneration in AD.
|
20308788 |
2010 |
|
Alzheimer's Disease
|
0.100 |
Biomarker
|
disease |
BEFREE |
These findings suggest a novel etiopathogenic mechanism of AD, which is initiated by the cleavage of I(2)(PP2A), producing I(2CTF), and describe a novel disease-relevant nontransgenic animal model of AD.
|
20651003 |
2010 |
|
Alzheimer's Disease
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Thus, our findings provide in vivo evidence that Hsp110 plays a critical function in tau phosphorylation state through maintenance of efficient PP2A activity, confirming its role in pathogenesis of Alzheimer's disease and other tauopathies.
|
20679486 |
2010 |
|
Alzheimer's Disease
|
0.100 |
Biomarker
|
disease |
BEFREE |
The two inhibitors of PP-2A, I (1) (PP2A) and I (2) (PP2A) , which are overexpressed in AD, might be responsible for the decreased phosphatase activity.
|
19184068 |
2009 |
|
Alzheimer's Disease
|
0.100 |
Biomarker
|
disease |
BEFREE |
This study highlights a novel signaling role of PP2A by Pin1 and implicates Pin1 as a therapeutic target to reduce aberrant phosphorylation of NF proteins in neurodegenerative disorders such as AD, PD, and ALS.
|
19940183 |
2009 |
|
Alzheimer's Disease
|
0.100 |
Biomarker
|
disease |
BEFREE |
This suggests that, in addition to kinases, PP2A and its regulatory subunits may be a therapeutic target for Alzheimer's disease.
|
19126401 |
2009 |
|
Alzheimer's Disease
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Altered PP2A activity has been implicated in spinocerebellar ataxia 12, Alzheimer's disease (AD), and other tauopathies.
|
18484086 |
2009 |
|
Alzheimer's Disease
|
0.100 |
Biomarker
|
disease |
BEFREE |
Taken together, these findings suggest that increased PP2A phosphorylation (Y307) can be mediated by Abeta deposition or oestrogen deficiency in the AD brain, and consequently compromise dephosphorylation of abnormally hyperphosphorylated tau, and lead to neurofibrillary tangle formation.
|
18208556 |
2008 |
|
Alzheimer's Disease
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Together, these findings suggested that the increased demethylation of PP2A (L309) mediated by Abeta overproduction or estrogen deficiency (ERalpha-/- and ERbeta-/-) may contribute to the reduced PP2A activity observed in the AD brain, resulting in the compromised dephosphorylation of abnormally hyperphosphorylated tau.
|
18586097 |
2008 |
|
Alzheimer's Disease
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Abnormal gene and protein expressions of PP2A, as well as its activity, were found to contribute to the abnormally prolonged Erk1/2 phosphorylation in the AD fibroblasts.
|
14678762 |
2003 |