title: Severe deficiency of the fatty acid amide hydrolase (FAAH) activity segregates with the Huntington's disease mutation in peripheral lymphocytes.
abstract: The search for peripheral markers of neurodegenerative diseases aims at identifying molecules that could help in monitoring the effects of future therapeutics in easily accessible cells. Here we focused on the involvement of the endocannabinoid system in Huntington's disease (HD). We assayed peripheral lymphocytes from HD patients and healthy controls, and found that the activity of the fatty acid amide hydrolase (FAAH), the enzyme that degrades the endocannabinoid anandamide (AEA), was dramatically decreased (down to less than 10%) in HD compared to healthy subjects. Concomitantly, the endogenous levels of AEA were approximately 6-fold higher in HD versus healthy lymphocytes, while the other elements of the endocannabinoid system were not affected by HD. Low FAAH activity in HD lymphocytes was not due to down-regulation of protein expression, but rather to blockage of enzyme activity by a cytosolic and irreversible inhibitor. Finally, pre-HD patients showed defective FAAH activity, as did the brain of HD patients compared with healthy controls. Taken together, our data indicate that FAAH activity in lymphocytes mirrors some of the metabolic changes which take place in the brain, it is a measurable non-genetic peripheral marker that segregates with the HD mutation, and it might serve as a target to test chemicals active on the widespread toxic effects of the mutant protein.
authors.affiliation: Department of Biomedical Sciences, University of Teramo, Piazza A Moro 45, Teramo, Italy.
authors.forename: Natalia
authors.initials: N
authors.lastname: Battista
authors.forename: Monica
authors.initials: M
authors.lastname: Bari
authors.forename: Alessia
authors.initials: A
authors.lastname: Tarditi
authors.forename: Caterina
authors.initials: C
authors.lastname: Mariotti
authors.forename: Anne-Catherine
authors.initials: AC
authors.lastname: Bachoud-Lévi
authors.forename: Chiara
authors.initials: C
authors.lastname: Zuccato
authors.forename: Alessandro
authors.initials: A
authors.lastname: Finazzi-Agrò
authors.forename: Silvia
authors.initials: S
authors.lastname: Genitrini
authors.forename: Marc
authors.initials: M
authors.lastname: Peschanski
authors.forename: Stefano
authors.initials: S
authors.lastname: Di Donato
authors.forename: Elena
authors.initials: E
authors.lastname: Cattaneo
authors.forename: Mauro
authors.initials: M
authors.lastname: Maccarrone
mesh_terms: D000328:Adult; D000581:Amidohydrolases / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D001692:Biological Transport; D015415:Biomarkers; D001921:Brain / Q000201:enzymology; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000235:genetics* / Q000378:metabolism*; D008214:Lymphocytes / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D043882:Receptors, Cannabinoid / Q000378:metabolism; D050916:TRPV Cation Channels / Q000378:metabolism; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D015415:Biomarkers; D043882:Receptors, Cannabinoid; D050916:TRPV Cation Channels; D000099252:Fatty Acid Amide Hydrolases; C494482:TRPV1 protein, human