PMID- 22720070
OWN - NLM
STAT- MEDLINE
DCOM- 20121213
LR  - 20240313
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 6
DP  - 2012
TI  - Epigenetic regulation of fatty acid amide hydrolase in Alzheimer disease.
PG  - e39186
LID - 10.1371/journal.pone.0039186 [doi]
LID - e39186
AB  - 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.
FAU - D'Addario, Claudio
AU  - D'Addario C
AD  - Department of Biomedical Sciences, University of Teramo, Teramo, Italy.
FAU - Di Francesco, Andrea
AU  - Di Francesco A
FAU - Arosio, Beatrice
AU  - Arosio B
FAU - Gussago, Cristina
AU  - Gussago C
FAU - Dell'Osso, Bernardo
AU  - Dell'Osso B
FAU - Bari, Monica
AU  - Bari M
FAU - Galimberti, Daniela
AU  - Galimberti D
FAU - Scarpini, Elio
AU  - Scarpini E
FAU - Altamura, A Carlo
AU  - Altamura AC
FAU - Mari, Daniela
AU  - Mari D
FAU - Maccarrone, Mauro
AU  - Maccarrone M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120612
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (DNA Primers)
RN  - EC 3.5.- (Amidohydrolases)
RN  - EC 3.5.1.- (fatty-acid amide hydrolase)
SB  - IM
MH  - Aged
MH  - Alzheimer Disease/*genetics
MH  - Amidohydrolases/*genetics
MH  - Base Sequence
MH  - DNA Primers
MH  - *Epigenesis, Genetic
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
PMC - PMC3373611
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2012/06/22 06:00
MHDA- 2012/12/14 06:00
PMCR- 2012/06/12
CRDT- 2012/06/22 06:00
PHST- 2012/03/23 00:00 [received]
PHST- 2012/05/21 00:00 [accepted]
PHST- 2012/06/22 06:00 [entrez]
PHST- 2012/06/22 06:00 [pubmed]
PHST- 2012/12/14 06:00 [medline]
PHST- 2012/06/12 00:00 [pmc-release]
AID - PONE-D-12-08802 [pii]
AID - 10.1371/journal.pone.0039186 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(6):e39186. doi: 10.1371/journal.pone.0039186. Epub 2012 Jun 12.