|
Alzheimer's Disease
|
0.300 |
PosttranslationalModification
|
disease |
BEFREE |
Because IRS1 and IRS2 signaling pathways are regulated through complex mechanisms including positive and negative feedback loops, whether the elevated phosphorylation of IRS1 at specific serine sites found in AD brains is a primary response to cognitive dysfunction remains unknown.
|
30964050 |
2019 |
|
Alzheimer's Disease
|
0.300 |
AlteredExpression
|
disease |
BEFREE |
Plasma neuronal-enriched extracellular vesicles (nEVs) of patients with AD were reported to exhibit elevated levels of phosphorylated (p) tau, Aβ42, and phosphorylated insulin receptor substrate 1 (IRS-1).
|
31305918 |
2019 |
|
Alzheimer's Disease
|
0.300 |
Biomarker
|
disease |
BEFREE |
Our findings suggest that the phosphorylation of IRS1 at specific Ser sites is a potential marker of Aβ-unrelated memory deficits caused by type 2 diabetes and aging; however, in Aβ-related memory decline, the modifications of IRS1 may be a marker of early detection of Aβ42 elevation prior to the onset of memory decline in AD.
|
31426549 |
2019 |
|
Alzheimer's Disease
|
0.300 |
Biomarker
|
disease |
BEFREE |
Brain protein O-GlcNAcylation is diminished in Alzheimer's disease (AD), and OGT targets include proteins of the insulin-signaling pathway (e.g., insulin receptor susbtrate-1, IRS-1).
|
29154269 |
2018 |
|
Alzheimer's Disease
|
0.300 |
AlteredExpression
|
disease |
BEFREE |
The expressions of IRS1, Aβ and Tuj in AD mice ileum were significantly different from WT mice (p<0.05).
|
28485801 |
2017 |
|
Alzheimer's Disease
|
0.300 |
AlteredExpression
|
disease |
BEFREE |
In the present work, we longitudinally analyze the age-dependent changes of (i) BVR-A protein levels and activation, (ii) total oxidative stress markers levels (PC, HNE, 3-NT) as well as (iii) IR/IRS1 levels and activation in the hippocampus of the triple transgenic model of AD (3xTg-AD) mice.
|
26698666 |
2016 |
|
Alzheimer's Disease
|
0.300 |
AlteredExpression
|
disease |
BEFREE |
We found that partial GLT-1 loss chronically increased Akt activation (reflected by increased phosphorylation at serine 473), impaired insulin signaling (reflected by decreased IRβ phosphorylation of tyrosines 1150/1151 and increased IRS-1 phosphorylation at serines 632/635 - denoted as 636/639 in humans), and reduced insulin degrading enzyme (IDE) activity in brains of mice expressing familial AβPPswe/PS1ΔE9 AD mutations.
|
25589729 |
2015 |
|
Alzheimer's Disease
|
0.300 |
PosttranslationalModification
|
disease |
BEFREE |
These results provide confirmation and specificity that abnormal phosphorylation of IRS1 is a pathological feature of AD and other tauopathies, and provide support for an association between insulin resistance and abnormal tau as well as amyloid-β.
|
25107476 |
2014 |
|
Alzheimer's Disease
|
0.300 |
GeneticVariation
|
disease |
BEFREE |
In conclusion, the Arg972 IRS1 polymorphism is an independent risk factor for AD and the A allele has a gene dosage effect on AD severity in Han Chinese.
|
24589556 |
2014 |
|
Alzheimer's Disease
|
0.300 |
Biomarker
|
disease |
BEFREE |
Brain insulin resistance thus appears to be an early and common feature of AD, a phenomenon accompanied by IGF-1 resistance and closely associated with IRS-1 dysfunction potentially triggered by Aβ oligomers and yet promoting cognitive decline independent of classic AD pathology.
|
22476197 |
2012 |
|
Alzheimer's Disease
|
0.300 |
Biomarker
|
disease |
RGD |
Changes in insulin-signaling transduction pathway underlie learning/memory deficits in an Alzheimer's disease rat model.
|
22527777 |
2012 |
|
Alzheimer's Disease
|
0.300 |
AlteredExpression
|
disease |
BEFREE |
Brain tissue from humans with AD had elevated levels of IRS-1pSer and activated JNK, analogous to what occurs in peripheral tissue in patients with diabetes.
|
22476196 |
2012 |
|
Alzheimer's Disease
|
0.300 |
Biomarker
|
disease |
BEFREE |
Feeding 3xTg-AD transgenic mice a diet high in saturated and omega-6 fat increased active JNK and phosphorylated IRS-1 and tau.
|
19605645 |
2009 |