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 (2.300.48) when compared to CT (1.000.14; *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: 0.750.04; LOAD: 1.110.15; *p<0.05) and activity (pmol/min per mg protein CT: 103.808.73; LOAD: 125.104.00; *p<0.05), as well as a reduction in DNA methylation at faah gene promoter (CT: 55.904.60%; LOAD: 41.204.90%; *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

Maccarrone M
2012

Abstract

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 (2.300.48) when compared to CT (1.000.14; *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: 0.750.04; LOAD: 1.110.15; *p<0.05) and activity (pmol/min per mg protein CT: 103.808.73; LOAD: 125.104.00; *p<0.05), as well as a reduction in DNA methylation at faah gene promoter (CT: 55.904.60%; LOAD: 41.204.90%; *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.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11697/156021
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