Pin1 contribution to Alzheimer's disease: transcriptional and epigenetic mechanisms in patients with late-onset Alzheimer's disease.
Neurodegener Dis
; 10(1-4): 207-11, 2012.
Article
in En
| MEDLINE
| ID: mdl-22261503
ABSTRACT
BACKGROUND:
Neurofibrillary tangles and senile plaques are hallmarks of Alzheimer's disease (AD) although the molecular basis of their coexistence remains elusive. The peptidyl-prolyl cis/trans isomerase Pin1 acts on both tau and amyloid precursor protein to regulate their functions by influencing tau phosphorylation and amyloid precursor protein processing.OBJECTIVE:
In order to identify potential biomarkers for AD in easily accessible cells and to gain insight into the relationship between the brain and peripheral compartments in AD pathology, we investigated Pin1 expression and activity in the peripheral blood mononuclear cells of subjects with late-onset AD (LOAD) and age-matched controls (CT).METHODS:
Gene and protein expression, promoter methylation, Ser(16) phosphorylation and activity of Pin1 were evaluated in 32 samples from subjects with LOAD and in 28 samples from CT.RESULTS:
In LOAD subjects, there was a statistically significant reduction in Ser(16) phosphorylation (-30%; p = 0.041) and promoter methylation (-8%; p = 0.001), whereas Pin1 expression was significantly increased (+74%; p = 0.018).CONCLUSION:
The modifications of Pin1 found in LOAD subjects support its involvement in the pathogenesis of the disease with an important role being played by epigenetic mechanisms.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Peptidylprolyl Isomerase
/
Genetic Predisposition to Disease
/
Epigenesis, Genetic
/
Alzheimer Disease
Type of study:
Observational_studies
Limits:
Aged
/
Aged80
/
Female
/
Humans
/
Male
Country/Region as subject:
Europa
Language:
En
Journal:
Neurodegener Dis
Journal subject:
NEUROLOGIA
Year:
2012
Type:
Article