scholarly journals GPR119 and GPR55 as Receptors for Fatty Acid Ethanolamides, Oleoylethanolamide and Palmitoylethanolamide

2021 ◽  
Vol 22 (3) ◽  
pp. 1034
Author(s):  
Dong-Soon Im
Keyword(s):  
Fatty Acid ◽  
Drug Discovery ◽  
Nuclear Receptors ◽  
Glucose Homeostasis ◽  
Membrane Receptors ◽  
Physiological Effects ◽  
Receptor Proteins ◽  
Fatty Acid Ethanolamides ◽  
Receptor Pharmacology ◽  
Anti Inflammation

Oleoylethanolamide and palmitoylethanolamide are members of the fatty acid ethanolamide family, also known as acylethanolamides. Their physiological effects, including glucose homeostasis, anti-inflammation, anti-anaphylactic, analgesia, and hypophagia, have been reported. They have affinity for different receptor proteins, including nuclear receptors such as PPARα, channels such as TRPV1, and membrane receptors such as GPR119 and GPR55. In the present review, the pathophysiological functions of fatty acid ethanolamides have been discussed from the perspective of receptor pharmacology and drug discovery.

scholarly journals Genetic Blockade of NAAA Cell-specifically Regulates Fatty Acid Ethanolamides (FAEs) Metabolism and Inflammatory Responses

2022 ◽  
Vol 12 ◽  
Author(s):  
Xiaohua Xie ◽  
Yitian Li ◽  
Sennan Xu ◽  
Pan Zhou ◽  
Longhe Yang ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Inflammatory Responses ◽  
Analgesic Effects ◽  
Fatty Acid Ethanolamides ◽  
A Cell ◽  
Anti Inflammatory ◽  
Inflammatory Phenotypes ◽  
Hydrolysis Of ◽  
Anti Inflammation

N-Acylethanolamine acid amidase (NAAA) is a lysosomal enzyme responsible for the hydrolysis of fatty acid ethanolamides (FAEs). However, the role of NAAA in FAEs metabolism and regulation of pain and inflammation remains mostly unknown. Here, we generated NAAA-deficient (NAAA-/-) mice using CRISPR-Cas9 technique, and found that deletion of NAAA increased PEA and AEA levels in bone marrow (BM) and macrophages, and elevated AEA levels in lungs. Unexpectedly, genetic blockade of NAAA caused moderately effective anti-inflammatory effects in lipopolysaccharides (LPS)-induced acute lung injury (ALI), and poor analgesic effects in carrageenan-induced hyperalgesia and sciatic nerve injury (SNI)-induced mechanical allodynia. These data contrasted with acute (single dose) or chronic NAAA inhibition by F96, which produced marked anti-inflammation and analgesia in these models. BM chimera experiments indicated that these phenotypes were associated with the absence of NAAA in non-BM cells, whereas deletion of NAAA in BM or BM-derived cells in rodent models resulted in potent analgesic and anti-inflammatory phenotypes. When combined, current study suggested that genetic blockade of NAAA regulated FAEs metabolism and inflammatory responses in a cell-specifical manner.

scholarly journals ONRLDB—manually curated database of experimentally validated ligands for orphan nuclear receptors: insights into new drug discovery

Database ◽  
2015 ◽  
Vol 2015 ◽  
pp. bav112 ◽  
Author(s):  
Ravikanth Nanduri ◽  
Isha Bhutani ◽  
Arun Kumar Somavarapu ◽  
Sahil Mahajan ◽  
Raman Parkesh ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Nuclear Receptors ◽  
Orphan Nuclear Receptors ◽  
New Drug

scholarly journals Binding of Androgen- and Estrogen-Like Flavonoids to Their Cognate (Non)Nuclear Receptors: A Comparison by Computational Prediction

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1613
Author(s):  
Giulia D’Arrigo ◽  
Eleonora Gianquinto ◽  
Giulia Rossetti ◽  
Gabriele Cruciani ◽  
Stefano Lorenzetti ◽  
...  
Keyword(s):  
Nuclear Receptors ◽  
Fruits And Vegetables ◽  
Computational Prediction ◽  
Membrane Receptors ◽  
Computational Docking ◽  
Docking Simulations ◽  
Mediated Effects ◽  
17Β Estradiol ◽  
G Protein Coupled ◽  
Relevant Degree

Flavonoids are plant bioactives that are recognized as hormone-like polyphenols because of their similarity to the endogenous sex steroids 17β-estradiol and testosterone, and to their estrogen- and androgen-like activity. Most efforts to verify flavonoid binding to nuclear receptors (NRs) and explain their action have been focused on ERα, while less attention has been paid to other nuclear and non-nuclear membrane androgen and estrogen receptors. Here, we investigate six flavonoids (apigenin, genistein, luteolin, naringenin, quercetin, and resveratrol) that are widely present in fruits and vegetables, and often used as replacement therapy in menopause. We performed comparative computational docking simulations to predict their capability of binding nuclear receptors ERα, ERβ, ERRβ, ERRγ, androgen receptor (AR), and its variant ART877A and membrane receptors for androgens, i.e., ZIP9, GPRC6A, OXER1, TRPM8, and estrogens, i.e., G Protein-Coupled Estrogen Receptor (GPER). In agreement with data reported in literature, our results suggest that these flavonoids show a relevant degree of complementarity with both estrogen and androgen NR binding sites, likely triggering genomic-mediated effects. It is noteworthy that reliable protein–ligand complexes and estimated interaction energies were also obtained for some suggested estrogen and androgen membrane receptors, indicating that flavonoids could also exert non-genomic actions. Further investigations are needed to clarify flavonoid multiple genomic and non-genomic effects. Caution in their administration could be necessary, until the safe assumption of these natural molecules that are largely present in food is assured.

Fatty Acid Synthesis as a Target for Antimalarial Drug Discovery

2005 ◽  
Vol 8 (1) ◽  
pp. 15-26 ◽  
Author(s):  
Jeff Lu ◽  
Patricia Lee ◽  
Norman Waters ◽  
Sean Prigge
Keyword(s):  
Fatty Acid ◽  
Drug Discovery ◽  
Fatty Acid Synthesis ◽  
Antimalarial Drug ◽  
Acid Synthesis

scholarly journals Mild Impairment of Mitochondrial OXPHOS Promotes Fatty Acid Utilization in POMC Neurons and Improves Glucose Homeostasis in Obesity

Cell Reports ◽  
2018 ◽  
Vol 25 (2) ◽  
pp. 383-397.e10 ◽  
Author(s):  
Katharina Timper ◽  
Lars Paeger ◽  
Carmen Sánchez-Lasheras ◽  
Luis Varela ◽  
Alexander Jais ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Glucose Homeostasis ◽  
Fatty Acid Utilization ◽  
Mild Impairment

Roles of fatty acid ethanolamides (FAE) in traumatic and ischemic brain injury

2014 ◽  
Vol 86 ◽  
pp. 26-31 ◽  
Author(s):  
Emanuela Esposito ◽  
Marika Cordaro ◽  
Salvatore Cuzzocrea
Keyword(s):  
Fatty Acid ◽  
Brain Injury ◽  
Ischemic Brain Injury ◽  
Ischemic Brain ◽  
Fatty Acid Ethanolamides
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