Severe deficiency of the fatty acid amide hydrolase (FAAH) activity segregates with the Huntington's disease mutation in peripheral lymphocytes

Natalia Battista, Monica Bari, Alessia Tarditi, Caterina Mariotti, Anne Catherine Bachoud-Lévi, Chiara Zuccato, Alessandro Finazzi-Agrò, Silvia Genitrini, Marc Peschanski, Stefano Di Donato, Elena Cattaneo, Mauro Maccarrone

Research output: Contribution to journalArticle

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 ∼ 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.

Original languageEnglish
Pages (from-to)108-116
Number of pages9
JournalNeurobiology of Disease
Volume27
Issue number1
DOIs
Publication statusPublished - Jul 2007

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Keywords

  • Endocannabinoid
  • Enzyme inhibition
  • FAAH
  • Huntington's disease
  • Lymphocyte

ASJC Scopus subject areas

  • Neurology

Cite this

Battista, N., Bari, M., Tarditi, A., Mariotti, C., Bachoud-Lévi, A. C., Zuccato, C., Finazzi-Agrò, A., Genitrini, S., Peschanski, M., Di Donato, S., Cattaneo, E., & Maccarrone, M. (2007). Severe deficiency of the fatty acid amide hydrolase (FAAH) activity segregates with the Huntington's disease mutation in peripheral lymphocytes. Neurobiology of Disease, 27(1), 108-116. https://doi.org/10.1016/j.nbd.2007.04.012