|
Alzheimer's Disease
|
0.100 |
Biomarker
|
disease |
BEFREE |
Thus, LMTK2 binds to KLC1 to direct axonal transport of p35 and its loss may contribute to Alzheimer's disease.
|
31068217 |
2019 |
|
Alzheimer's Disease
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
An increased level of the p25 activator of CDK5 kinase was found in AD-PHF-injected 5xFAD mice.
|
30599077 |
2019 |
|
Alzheimer's Disease
|
0.100 |
Biomarker
|
disease |
BEFREE |
Our findings demonstrate sex differences in the effects of p35 reduction on biochemical pathways relevant to the modulation of Aβ plaque deposition and confirm the importance of examining both sexes in preclinical AD research.
|
31421203 |
2019 |
|
Alzheimer's Disease
|
0.100 |
Biomarker
|
disease |
BEFREE |
An inducible mouse model of p25 accumulation (the CK-p25 mouse) that displays key pathological hallmarks of Alzheimer disease (AD) is used as a gold-standard to test the proposed algorithm by providing a conditional control of rapid neurodegeneration.
|
29723637 |
2018 |
|
Alzheimer's Disease
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Our results suggest that the downregulation of the miR-15/107 family might have a role in the pathogenesis of AD by increasing the levels of CDK5R1/p35 and consequently enhancing CDK5 activity.
|
27343180 |
2017 |
|
Alzheimer's Disease
|
0.100 |
Biomarker
|
disease |
BEFREE |
Deregulation of Cyclin-dependent kinase 5 (Cdk5) activity by production of its hyperactivator p25 is involved in the formation of tau and amyloid pathology reminiscent of Alzheimer's disease (AD).
|
29036814 |
2017 |
|
Alzheimer's Disease
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Cyclin-dependent kinase 5 (Cdk5), which binds to and is activated by p35, phosphorylates multiple substrates and plays an essential role in the development and function of the CNS; however, proteolytic production of p25 from p35 under stress conditions leads to the inappropriate activation of Cdk5 and contributes to hyperphosphorylation of τ and other substrates that are related to the pathogenesis of Alzheimer's disease.
|
28420695 |
2017 |
|
Alzheimer's Disease
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
These results reveal a link between p25 and BACE1 in AD brains and suggest that upregulated Cdk5 activation by p25 accelerates AD pathogenesis by enhancing BACE1 activity via phosphorylation.
|
26317805 |
2015 |
|
Alzheimer's Disease
|
0.100 |
Biomarker
|
disease |
BEFREE |
Together, these results reveal a physiological role of p25 production in synaptic plasticity and memory and provide new insights into the function of p25 in Aβ-associated neurotoxicity and AD-like pathology.
|
24725413 |
2014 |
|
Alzheimer's Disease
|
0.100 |
Biomarker
|
disease |
BEFREE |
While patients with severe AD did display a consistent reduction in p23 levels, our inability to observe p19 in mouse or human AD brain samples suggests that the usefulness of the p23 neo-epitope antibody is restricted to cells and primary neurons undergoing cellular stress.
|
21691801 |
2012 |
|
Alzheimer's Disease
|
0.100 |
Biomarker
|
disease |
BEFREE |
The deregulation of cyclin-dependent kinase 5 (Cdk5) by p25 has been shown to contribute to the pathogenesis in a number of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD) and Alzheimer's disease (AD).
|
22262900 |
2012 |
|
Alzheimer's Disease
|
0.100 |
Biomarker
|
disease |
BEFREE |
The involvement of Cdk5 activator p35 in social isolation-triggered onset of early Alzheimer's disease-related cognitive deficit in the transgenic mice.
|
21544067 |
2011 |
|
Alzheimer's Disease
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Here, we tested the early compensation hypothesis by analyzing the levels of p25 and its precursor p35 in AD postmortem samples from different brain regions at different stages of tau pathology, using quantitative Western blots.
|
21616478 |
2011 |
|
Alzheimer's Disease
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
The calpain-mediated cleavage of p35 to p25 and the resulting aberrant activity and neurotoxicity of Cdk5 have been implicated in neurological disorders, such as Alzheimer's disease.
|
21338355 |
2011 |
|
Alzheimer's Disease
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
This review focuses on the role of carotenoids like retinoic acid (RA), all trans retinoic acid (ATRA), lycopene and β-carotene in prevention of AD symptoms primarily through inhibition of amyloid beta (Aβ) formation, deposition and fibril formation either by reducing the levels of p35 or inhibiting corresponding enzymes.
|
21672580 |
2011 |
|
Alzheimer's Disease
|
0.100 |
Biomarker
|
disease |
BEFREE |
In this study, we examined whether p25 was linked to altered neurotransmitter release in AD.
|
20033852 |
2010 |
|
Alzheimer's Disease
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Subjects carrying both the CDK5R1 (3'-UTR, rs735555) AA genotype and the GSK-3beta (-50, rs334558) CC genotype had a 12.5-fold decrease in AD risk (adjusted by age, sex and APOE status OR = 0.08, 95% CI = 0.01-0.76, P = 0.03), suggesting synergistic effects (epistasis) between both genes.
|
19154537 |
2009 |
|
Alzheimer's Disease
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Furthermore, the steady-state p23 levels are reduced in the brains of individuals with AD.
|
18652896 |
2008 |
|
Alzheimer's Disease
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
By extensive genetic analysis of the genes encoding CDK5 (CDK5), p35 (CDK5R1) and p39 (CDK5R2), we excluded causal mutations in 70 familial early-onset AD patients.
|
15917097 |
2005 |
|
Alzheimer's Disease
|
0.100 |
GeneticVariation
|
disease |
LHGDN |
By extensive genetic analysis of the genes encoding CDK5 (CDK5), p35 (CDK5R1) and p39 (CDK5R2), we excluded causal mutations in 70 familial early-onset AD patients.
|
15917097 |
2005 |
|
Alzheimer's Disease
|
0.100 |
Biomarker
|
disease |
BEFREE |
Therefore, p25 formation may initially be a compensatory response for early learning deficits in Alzheimer's disease, but continued formation could contribute to detrimental changes in Alzheimer's disease.
|
16237316 |
2005 |
|
Alzheimer's Disease
|
0.100 |
Biomarker
|
disease |
BEFREE |
Cdk5 phosphorylates tau at AD-specific phospho-epitopes when it associates with p25. p25 is a truncated activator, which is produced from the physiological Cdk5 activator p35 upon exposure to Abeta peptides.
|
15592431 |
2005 |
|
Alzheimer's Disease
|
0.100 |
Biomarker
|
disease |
BEFREE |
Glucose-induced expression of the cyclin-dependent protein kinase 5 activator p35 involved in Alzheimer's disease regulates insulin gene transcription in pancreatic beta-cells.
|
14976144 |
2004 |
|
Alzheimer's Disease
|
0.100 |
Biomarker
|
disease |
LHGDN |
Brain levels of CDK5 activator p25 are not increased in Alzheimer's or other neurodegenerative diseases with neurofibrillary tangles.
|
12859671 |
2003 |
|
Alzheimer's Disease
|
0.100 |
PosttranslationalModification
|
disease |
LHGDN |
Truncation of CDK5 activator p35 induces intensive phosphorylation of Ser202/Thr205 of human tau.
|
12226093 |
2002 |