Objective: Alzheimer disease (AD) is a progressive, degenerative and irreversible neurological disorder with few therapies available. In search for new potential targets, increasing evidence suggests a role for the endocannabinoid system (ECS) in the regulation of neurodegenerative processes. Methods: We have studied the gene expression status and the epigenetic regulation of ECS components in peripheral blood mononuclear cells (PBMCs) of subjects with late-onset AD (LOAD) and age-matched controls (CT). Results: We found an increase in fatty acid amide hydrolase (faah) gene expression in LOAD subjects (2.30 +/- 0.48) when compared to CT (1.00 +/- 0.14; *p<0.05) and no changes in the mRNA levels of any other gene of ECS elements. Consistently, we also observed in LOAD subjects an increase in FAAH protein levels (CT: 0.75 +/- 0.04; LOAD: 1.11 +/- 0.15; *p<0.05) and activity (pmol/min per mg protein CT: 103.80 +/- 8.73; LOAD: 125.10 +/- 4.00; *p<0.05), as well as a reduction in DNA methylation at faah gene promoter (CT: 55.90 +/- 4.60%; LOAD: 41.20 +/- 4.90%; *p<0.05). Conclusions: Present findings suggest the involvement of FAAH in the pathogenesis of AD, highlighting the importance of epigenetic mechanisms in enzyme regulation; they also point to FAAH as a new potential biomarker for AD in easily accessible peripheral cells.
Epigenetic regulation of fatty acid amide hydrolase in Alzheimer disease / C. D'Addario, A. Di Francesco, B. Arosio, C. Gussago, B. Dell'Osso, M. Bari, D. Galimberti, E. Scarpini, A.C. Altamura, D. Mari, M. Maccarrone. - In: PLOS ONE. - ISSN 1932-6203. - 7:6(2012), pp. e39186.1-e39186.7.
|Titolo:||Epigenetic regulation of fatty acid amide hydrolase in Alzheimer disease|
MARI, DANIELA (Penultimo)
|Parole Chiave:||cannabinoid receptor-binding; central-nervous-system; endocannabinoid system; DNA methylation; messenger-RNA; anandamide; expression; cells; brain; CB1|
|Settore Scientifico Disciplinare:||Settore MED/09 - Medicina Interna|
|Data di pubblicazione:||2012|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1371/journal.pone.0039186|
|Appare nelle tipologie:||01 - Articolo su periodico|