The role of fatty acid amide hydrolase enzyme inhibitors in Alzheimer's disease

2021 ◽  
Author(s):  
Smita Jain ◽  
Akansha Bisht ◽  
Kanika Verma ◽  
Swarnima Negi ◽  
Sarvesh Paliwal ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Fatty Acid ◽  
Enzyme Inhibitors ◽  
Fatty Acid Amide Hydrolase ◽  
Acid Amide ◽  
Amide Hydrolase ◽  
Fatty Acid Amide

scholarly journals Anti-Inflammatory Effects of Fatty Acid Amide Hydrolase Inhibition in Monocytes/Macrophages from Alzheimer’s Disease Patients

Biomolecules ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 502
Author(s):  
Valerio Chiurchiù ◽  
Lucia Scipioni ◽  
Beatrice Arosio ◽  
Daniela Mari ◽  
Sergio Oddi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Fatty Acid ◽  
Cannabinoid Receptors ◽  
Fatty Acid Amide Hydrolase ◽  
Acid Amide ◽  
Anti Inflammatory ◽  
Amide Hydrolase ◽  
Fatty Acid Amide

Growing evidence shows that the immune system is critically involved in Alzheimer’s disease (AD) pathogenesis and progression. The modulation and targeting of peripheral immune mechanisms are thus promising therapeutic or preventive strategies for AD. Given the critical involvement of the endocannabinoid (eCB) system in modulating immune functions, we investigated the potential role of the main elements of such a system, namely type-1 and type-2 cannabinoid receptors (CB1 and CB2), and fatty acid amide hydrolase (FAAH), in distinct immune cell populations of the peripheral blood of AD patients. We found that, compared to healthy controls, CB1 and CB2 expression was significantly lower in the B-lymphocytes of AD patients. Moreover, we found that CB2 was significantly lower and FAAH was significantly higher in monocytes of the same subjects. In contrast, T-lymphocytes and NK cells did not show any variation in any of these proteins. Of note, monocytic CB2 and FAAH levels significantly correlated with clinical scores. Furthermore, the pharmacological inactivation of FAAH in monocytes and monocyte-derived macrophages obtained from AD patients was able to modulate their immune responses, by reducing production of pro-inflammatory cytokines such as TNF-α, IL-6 and IL-12, and enhancing that of the anti-inflammatory cytokine IL-10. Furthermore, FAAH blockade skewed AD monocyte-derived macrophages towards a more anti-inflammatory and pro-resolving phenotype. Collectively, our findings highlight a central role of FAAH in regulating AD monocytes/macrophages that could be of value in developing novel monocyte-centered therapeutic approaches aimed at promoting a neuroprotective environment.

scholarly journals Cannabinoid CB2Receptors and Fatty Acid Amide Hydrolase Are Selectively Overexpressed in Neuritic Plaque-Associated Glia in Alzheimer's Disease Brains

2003 ◽  
Vol 23 (35) ◽  
pp. 11136-11141 ◽  
Author(s):  
Cristina Benito ◽  
Estefanía Núñez ◽  
Rosa M. Tolón ◽  
Erica J. Carrier ◽  
Alberto Rábano ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Fatty Acid ◽  
Fatty Acid Amide Hydrolase ◽  
Acid Amide ◽  
Neuritic Plaque ◽  
Amide Hydrolase ◽  
Fatty Acid Amide

scholarly journals Elevated Brain Fatty Acid Amide Hydrolase Induces Depressive-Like Phenotypes in Rodent Models: A Review

2021 ◽  
Vol 22 (3) ◽  
pp. 1047
Author(s):  
Dorsa Rafiei ◽  
Nathan J. Kolla
Keyword(s):  
Depressive Symptoms ◽  
Fatty Acid ◽  
Animal Models ◽  
Fatty Acid Amide Hydrolase ◽  
Acid Amide ◽  
Endocannabinoid System ◽  
Animal Models Of Depression ◽  
Amide Hydrolase ◽  
Fatty Acid Amide

Altered activity of fatty acid amide hydrolase (FAAH), an enzyme of the endocannabinoid system, has been implicated in several neuropsychiatric disorders, including major depressive disorder (MDD). It is speculated that increased brain FAAH expression is correlated with increased depressive symptoms. The aim of this scoping review was to establish the role of FAAH expression in animal models of depression to determine the translational potential of targeting FAAH in clinical studies. A literature search employing multiple databases was performed; all original articles that assessed FAAH expression in animal models of depression were considered. Of the 216 articles that were screened for eligibility, 24 articles met inclusion criteria and were included in this review. Three key findings emerged: (1) FAAH expression is significantly increased in depressive-like phenotypes; (2) genetic knockout or pharmacological inhibition of FAAH effectively reduces depressive-like behavior, with a dose-dependent effect; and (3) differences in FAAH expression in depressive-like phenotypes were largely localized to animal prefrontal cortex, hippocampus and striatum. We conclude, based on the animal literature, that a positive relationship can be established between brain FAAH level and expression of depressive symptoms. In summary, we suggest that FAAH is a tractable target for developing novel pharmacotherapies for MDD.

scholarly journals Suppression of acute and anticipatory nausea by peripherally restricted fatty acid amide hydrolase inhibitor in animal models: role of PPARα and CB1 receptors

2017 ◽  
Vol 174 (21) ◽  
pp. 3837-3847 ◽  
Author(s):  
Erin M Rock ◽  
Guillermo Moreno-Sanz ◽  
Cheryl L Limebeer ◽  
Gavin N Petrie ◽  
Roberto Angelini ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Animal Models ◽  
Fatty Acid Amide Hydrolase ◽  
Acid Amide ◽  
Cb1 Receptors ◽  
Anticipatory Nausea ◽  
Amide Hydrolase ◽  
Fatty Acid Amide

Role of the basolateral amygdala in mediating the effects of the fatty acid amide hydrolase inhibitor URB597 on HPA axis response to stress

2014 ◽  
Vol 24 (9) ◽  
pp. 1511-1523 ◽  
Author(s):  
Gaurav Bedse ◽  
Roberto Colangeli ◽  
Angelo M. Lavecchia ◽  
Adele Romano ◽  
Fabio Altieri ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Hpa Axis ◽  
Basolateral Amygdala ◽  
Fatty Acid Amide Hydrolase ◽  
Acid Amide ◽  
Response To Stress ◽  
Amide Hydrolase ◽  
Fatty Acid Amide

scholarly journals Role of Steroids on the Membrane Binding Ability of Fatty Acid Amide Hydrolase

2019 ◽  
Vol 4 (1) ◽  
pp. 42-50 ◽  
Author(s):  
Annalaura Sabatucci ◽  
Monica Simonetti ◽  
Daniel Tortolani ◽  
Clotilde B. Angelucci ◽  
Enrico Dainese ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Amide Hydrolase ◽  
Membrane Binding ◽  
Acid Amide ◽  
Binding Ability ◽  
Amide Hydrolase ◽  
Fatty Acid Amide

Role of Fatty Acid Amide Hydrolase in the Transport of the Endogenous Cannabinoid Anandamide

2001 ◽  
Vol 59 (6) ◽  
pp. 1369-1375 ◽  
Author(s):  
Theresa A. Day ◽  
Fariborz Rakhshan ◽  
Dale G. Deutsch ◽  
Eric L. Barker
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Amide Hydrolase ◽  
Acid Amide ◽  
Amide Hydrolase ◽  
Endogenous Cannabinoid ◽  
Fatty Acid Amide

scholarly journals The role of fatty acid amide hydrolase inhibition in nicotine reward and dependence

Life Sciences ◽  
2013 ◽  
Vol 92 (8-9) ◽  
pp. 458-462 ◽  
Author(s):  
Pretal P. Muldoon ◽  
Aron H. Lichtman ◽  
Loren H. Parsons ◽  
M. Imad Damaj
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Amide Hydrolase ◽  
Acid Amide ◽  
Amide Hydrolase ◽  
Fatty Acid Amide
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