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palmitoylethanolamide

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https://www.readbyqxmd.com/read/27916440/characterisation-of-peroxisome-proliferator-activated-receptor-signalling-in-the-midbrain-periaqueductal-grey-of-rats-genetically-prone-to-heightened-stress-negative-affect-and-hyperalgesia
#1
Bright N Okine, Jessica C Gaspar, Manish K Madasu, Weredeselam M Olango, Brendan Harhen, Michelle Roche, David P Finn
The stress-hyperresponsive Wistar-Kyoto (WKY) rat strain exhibits a hyperalgesic phenotype and is a useful genetic model for studying stress-pain interactions. Peroxisome proliferator-activated receptor (PPAR) signalling in the midbrain periaqueductal grey (PAG) modulates pain. This study characterised PPAR signalling in the PAG of WKY rats exposed to the formalin test of inflammatory pain, versus Sprague-Dawley (SD) controls. Formalin injection reduced levels of the endogenous PPAR ligands N-palmitoylethanolamide (PEA) and N-oleoylethanolamide (OEA) in the lateral(l) PAG of SD rats, but not WKY rats which exhibited higher levels of these analytes compared with formalin-injected SD counterparts...
December 1, 2016: Brain Research
https://www.readbyqxmd.com/read/27915171/progress-in-the-development-of-%C3%AE-lactams-as-n-acylethanolamine-acid-amidase-naaa-inhibitors-synthesis-and-sar-study-of-new-potent-n-o-substituted-derivatives
#2
R Petracca, S Ponzano, S M Bertozzi, O Sasso, D Piomelli, T Bandiera, F Bertozzi
The anti-inflammatory effects resulting from raising the levels of palmitoylethanolamide (PEA), an endogenous bioactive lipid, led to envisage N-Acylethanolamine Acid Amidase (NAAA), the cysteine hydrolase mainly responsible for PEA degradation, as an attractive target for small molecule inhibitors. Previous work in our group identified serine-derived β-lactams as potent and systemically active inhibitors of NAAA activity. Aiming to expand the SAR study around this class of compounds, we investigated the effect of the substitution on the endocyclic nitrogen by designing and synthesizing a series of N-substituted β-lactams...
November 23, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27911411/preparation-and-in-vivo-use-of-an-activity-based-probe-for-n-acylethanolamine-acid-amidase
#3
Elisa Romeo, Silvia Pontis, Stefano Ponzano, Fabiola Bonezzi, Marco Migliore, Simona Di Martino, Maria Summa, Daniele Piomelli
Activity-based protein profiling (ABPP) is a method for the identification of an enzyme of interest in a complex proteome through the use of a chemical probe that targets the enzyme's active sites. A reporter tag introduced into the probe allows for the detection of the labeled enzyme by in-gel fluorescence scanning, protein blot, fluorescence microscopy, or liquid chromatography-mass spectrometry. Here, we describe the preparation and use of the compound ARN14686, a click chemistry activity-based probe (CC-ABP) that selectively recognizes the enzyme N-acylethanolamine acid amidase (NAAA)...
November 23, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27871881/targeting-brain-and-peripheral-plasticity-of-the-lipidome-in-acute-kainic-acid-induced-epileptic-seizures-in-mice-via-quantitative-mass-spectrometry
#4
Raissa Lerner, Julia Post, Sebastian Loch, Beat Lutz, Laura Bindila
Epilepsy is a highly common chronic neurological disorder, manifested in many different types, affecting ~1% of the worldwide human population. The molecular mechanisms of epileptogenesis has not yet been clarified, and pharmacoresistance exhibited by 30-40% of epilepsy patients remains a major obstacle in medical care. Growing evidence indicates a role of lipid signalling pathways in epileptogenesis, thus lipid signals emerge as potential biomarkers for the onset and evolving course of the epileptic disorder, as well as potential therapeutic agents and targets...
November 15, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27847471/maternal-caloric-restriction-implemented-during-the-preconceptional-and-pregnancy-period-alters-hypothalamic-and-hippocampal-endocannabinoid-levels-at-birth-and-induces-overweight-and-increased-adiposity-at-adulthood-in-male-rat-offspring
#5
María Teresa Ramírez-López, Mariam Vázquez, Laura Bindila, Ermelinda Lomazzo, Clementine Hofmann, Rosarío Noemí Blanco, Francisco Alén, María Antón, Juan Decara, Rocío Arco, Daniel Ouro, Laura Orio, Juan Suárez, Beat Lutz, Raquel Gómez de Heras, Fernando Rodríguez de Fonseca
Exposure to inadequate nutritional conditions in critical windows of development has been associated to disturbances on metabolism and behavior in the offspring later in life. The role of the endocannabinoid system, a known regulator of energy expenditure and adaptive behaviors, in the modulation of these processes is unknown. In the present study, we investigated the impact of exposing rat dams to diet restriction (20% less calories than standard diet) during pre-gestational and gestational periods on: (a) neonatal outcomes; (b) endocannabinoid content in hypothalamus, hippocampus and olfactory bulb at birth; (c) metabolism-related parameters; and (d) behavior in adult male offspring...
2016: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/27790149/co-micronized-palmitoylethanolamide-polydatin-treatment-causes-endometriotic-lesion-regression-in-a-rodent-model-of-surgically-induced-endometriosis
#6
Rosanna Di Paola, Roberta Fusco, Enrico Gugliandolo, Rosalia Crupi, Maurizio Evangelista, Roberta Granese, Salvatore Cuzzocrea
Endometriosis is a chronic, painful disease characterized by the presence of endometrial glands and stroma outside the uterine cavity. Palmitoylethanolamide (PEA), an endogenous fatty acid amide, has anti-inflammatory and neuroprotective effects. PEA lacks free radical scavenging activity, unlike polydatin (PLD), a natural precursor of resveratrol. The aim of this study was to investigate the effect of orally administered co-micronized PEA/polydatin [m(PEA/PLD)] in an autologous rat model of surgically induced endometriosis...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27757050/new-topical-treatment-of-vulvodynia-based-on-the-pathogenetic-role-of-cross-talk-between-nociceptors-immunocompetent-cells-and-epithelial-cells
#7
J M Keppel Hesselink, D J Kopsky, N Sajben
Topical treatments of localized neuropathic pain syndromes in general are mostly neglected, mainly due to the fact that most pain physicians expect that a topical formulation needs to result in a transdermal delivery of the active compounds. On the basis of the practical experience, this study brings forth a new, somewhat neglected element of the vulvodynia pathogenesis: the cross talk between the nerve endings of nociceptors, the adjacent immunocompetent cells, and vaginal epithelial cells. Insight into this cross talk during a pathogenic condition supports the treatment of vulvodynia with topical (compounded) creams...
2016: Journal of Pain Research
https://www.readbyqxmd.com/read/27756691/endocannabinoids-and-sleep
#8
REVIEW
Oscar Prospéro-García, Octavio Amancio-Belmont, Alline L Becerril Meléndez, Alejandra E Ruiz-Contreras, Mónica Méndez-Díaz
Sleep is regulated by several brain structures, neurotransmitters and neuromodulators. Endocannabinoids (eCBs) are a group of lipids with modulatory activity in the brain and bind mainly to cannabinoid receptors CB1R and CB2R, thereby modulating several brain functions, (memory, mood, food intake, pain perception). Oleoylethanolamide and palmitoylethanolamide belong to the N-acylethanolamides (NAEs) family, another type of active endogenous lipids. They bind to the peroxisome proliferator-activated receptor α but not to CB1R, thereby modulating food satiety, inflammation and pain...
December 2016: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/27729772/resolvins-and-aliamides-lipid-autacoids-in-ophthalmology-what-promise-do-they-hold
#9
REVIEW
Jan M Keppel Hesselink, Flavia Chiosi, Ciro Costagliola
Resolvins are a novel class of lipid-derived endogenous molecules (autacoids) with potent immunomodulating properties, which regulate the resolution phase of an active immune response. These modulating factors are locally produced, influencing the function of cells and/or tissues, which are produced on demand and subsequently metabolized in the same cells and/or tissues. This review is focused on certain lipid autacoids with putative relevance for ophthalmology in general and for dry eye more specifically. We also briefly investigate the concept of aliamides and the role of palmitoylethanolamide in ophthalmology, and analyze in more detail the putative role and the preclinical and clinical development of resolvins as emerging treatments for dry eye and related disorders, with a focus on one of the lead resolvin derivatives - RX-10045...
2016: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/27720681/palmitoylethanolamide-reduces-inflammation-and-itch-in-a-mouse-model-of-contact-allergic-dermatitis
#10
Massimo Vaia, Stefania Petrosino, Daniele De Filippis, Luana Negro, Andrea Guarino, Rosa Carnuccio, Vincenzo Di Marzo, Teresa Iuvone
In mice, 2,4-dinitrofluorobenzene (DNFB) induces contact allergic dermatitis (CAD), which, in a late phase, is characterized by mast cell (MC) infiltration and angiogenesis. Palmitoylethanolamide (PEA), an endogenous anti-inflammatory molecule, acts by down-modulating MCs following activation of the cannabinoid CB2 receptor and peroxisome proliferator-activated receptor-α (PPAR-α). We have previously reported the anti-inflammatory effect of PEA in the early stage of CAD. Here, we examined whether PEA reduces the features of the late stage of CAD including MC activation, angiogenesis and itching...
October 5, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27701827/beneficial-effects-of-co-ultramicronized-palmitoylethanolamide-luteolin-in-a-mouse-model-of-autism-and-in-a-case-report-of-autism
#11
Bartolomeo Bertolino, Rosalia Crupi, Daniela Impellizzeri, Giuseppe Bruschetta, Marika Cordaro, Rosalba Siracusa, Emanuela Esposito, Salvatore Cuzzocrea
AIMS: Autism spectrum disorder (ASD) is a condition defined by social communication deficits and repetitive restrictive behaviors. Association of the fatty acid amide palmitoylethanolamide (PEA) with the flavonoid luteolin displays neuroprotective and antiinflammatory actions in different models of central nervous system pathologies. We hypothesized that association of PEA with luteolin might have therapeutic utility in ASD, and we employed a well-recognized autism animal model, namely sodium valproate administration, to evaluate cognitive and motor deficits...
October 4, 2016: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/27693242/a-quantitative-study-on-splice-variants-of-n-acylethanolamine-acid-amidase-in-human-prostate-cancer-cells-and-other-cells
#12
Yuma Sakura, Kazuhito Tsuboi, Toru Uyama, Xia Zhang, Rikiya Taoka, Mikio Sugimoto, Yoshiyuki Kakehi, Natsuo Ueda
N-Acylethanolamine acid amidase (NAAA) is a lysosomal enzyme, hydrolyzing various bioactive N-acylethanolamines with a preference for palmitoylethanolamide. Human NAAA mRNA was previously reported to consist of multiple 3'-end splice variants. However, their tissue distributions and roles have not been examined yet. In the present study, we first identified four major splice variants (tentatively referred to as a1, a2, b2, and c2) in a human prostate cancer cell line LNCaP, which were composed of exons 1-11, exons 1-10 and 12, exons 1-9 and 12, and exons 1-8 and 12, respectively...
December 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27649266/n-palmitoylethanolamide-in-the-anterior-cingulate-cortex-attenuates-inflammatory-pain-behaviour-indirectly-via-a-cb1-receptor-mediated-mechanism
#13
Bright N Okine, Manish K Madasu, Fiona McGowan, Charles Prendergast, Jessica C Gaspar, Brendan Harhen, Michelle Roche, David P Finn
The neural substrates and mechanisms mediating the antinociceptive effects of the endogenous bioactive lipid, N-palmitoylethanolamide (PEA), require further investigation. We investigated the effects of exogenous PEA administration into the anterior cingulate cortex (ACC), an important brain region linked with cognitive and affective modulation of pain, on formalin-evoked nociceptive behaviour in rats. Potential involvement of peroxisome proliferator-activated receptor isoforms (PPAR) α and γ or endocannabinoid-mediated entourage effects at cannabinoid1 (CB1) receptors or transient receptor potential subfamily V member 1 (TRPV1) in mediating the effects of PEA was also investigated...
August 16, 2016: Pain
https://www.readbyqxmd.com/read/27637550/calcium-dependent-generation-of-n-acylethanolamines-and-lysophosphatidic-acids-by-glycerophosphodiesterase-gde7
#14
Iffat Ara Sonia Rahman, Kazuhito Tsuboi, Zahir Hussain, Ryouhei Yamashita, Yoko Okamoto, Toru Uyama, Naoshi Yamazaki, Tamotsu Tanaka, Akira Tokumura, Natsuo Ueda
N-Acylethanolamines form a class of lipid mediators and include an endocannabinoid arachidonoylethanolamide (anandamide), analgesic and anti-inflammatory palmitoylethanolamide, and appetite-suppressing oleoylethanolamide. In animal tissues, N-acylethanolamines are synthesized from N-acylated ethanolamine phospholipids directly by N-acylphosphatidylethanolamine-hydrolyzing phospholipase D or through multi-step pathways via N-acylethanolamine lysophospholipids. We previously reported that glycerophosphodiesterase (GDE) 4, a member of the GDE family, has lysophospholipase D (lysoPLD) activity hydrolyzing N-acylethanolamine lysophospholipids to N-acylethanolamines...
December 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27625036/adelmidrol-a-palmitoylethanolamide-analogue-as-a-new-pharmacological-treatment-for-the-management-of-inflammatory-bowel-disease
#15
Marika Cordaro, Daniela Impellizzeri, Enrico Gugliandolo, Rosalba Siracusa, Rosalia Crupi, Emanuela Esposito, Salvatore Cuzzocrea
Leukocyte infiltration, improved levels of intercellular adhesion molecule 1 (ICAM-1), and oxidative stress in the colon are the principal factors in inflammatory bowel disease. The goal of the current study was to explore the effects of adelmidrol, an analog of the anti-inflammatory fatty acid amide signaling molecule palmitoylethanolamide, in mice subjected to experimental colitis. Additionally, to clarify whether the protective action of adelmidrol is dependent on the activation of peroxisome proliferator-activated receptors (PPARs), we investigated the effects of a PPARγ antagonist, GW9662, on adelmidrol action...
November 2016: Molecular Pharmacology
https://www.readbyqxmd.com/read/27616549/palmitoylethanolamide-protects-mice-against-6-ohda-induced-neurotoxicity-and-endoplasmic-reticulum-stress-in-vivo-and-in-vitro-evidence
#16
Carmen Avagliano, Roberto Russo, Carmen De Caro, Claudia Cristiano, Giovanna La Rana, Giuseppe Piegari, Orlando Paciello, Rita Citraro, Emilio Russo, Giovambattista De Sarro, Rosaria Meli, Giuseppina Mattace Raso, Antonio Calignano
Several pathogenetic factors have been involved in the onset and progression of Parkinson's disease (PD), including inflammation, oxidative stress, unfolded protein accumulation, and apoptosis. Palmitoylethanolamide (PEA), an endogenous N-acylethanolamine, has been shown to be a neuroprotective and anti-inflammatory molecule, acting as a peroxisome proliferator activated receptor (PPAR)-α agonist. In this study we investigated the effects of PEA on behavioral alterations and the underlying pathogenic mechanisms in the 6-hydroxydopamine (6-OHDA)-induced model of PD in male mice...
September 8, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27608657/palmitoylethanolamide-reverses-paclitaxel-induced-allodynia-in-mice
#17
Giulia Donvito, Jenny L Wilkerson, M Imad Damaj, Aron H Lichtman
Chemotherapy-induced peripheral neuropathy (CIPN) represents a serious complication associated with antineoplastic drugs. Although there are no medications available that effectively prevent CIPN, many classes of drugs have been used to treat this condition, including anticonvulsants, serotonin and noradrenaline reuptake inhibitors, and opioids. However, these therapeutic options yielded inconclusive results in CIPN clinical trials and produced assorted side effects with their prolonged use. Thus, there is an urgent need to develop efficacious and safe treatments for CIPN...
November 2016: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/27599446/adelmidrol-a-palmitoylethanolamide-analogue-as-a-new-pharmacological-treatment-for-the-management-of-acute-and-chronic-inflammation
#18
Daniela Impellizzeri, Rosanna Di Paola, Marika Cordaro, Enrico Gugliandolo, Giovanna Casili, Valeria Maria Morittu, Domenico Britti, Emanuela Esposito, Salvatore Cuzzocrea
The aim of study was to examine the anti-inflammatory and analgesic effects of adelmidrol, an analogue of palmitoylethanolamide (PEA), in animal models of acute and chronic inflammation [carrageenan-induced paw edema (CAR) and collagen-induced arthritis (CIA)]. In order to elucidate whether the action of adelmidrol is related to activation of peroxisome proliferator-activated receptors (PPAR-α or PPAR-γ), we investigated the effects of PPAR-γ antagonist, GW9662 on adelmidrol mechanism. CAR induced paw edema, hyperalgesia and the activation of pro-inflammatory NF-κB pathway were markedly reduced by treatment with adelmidrol...
November 1, 2016: Biochemical Pharmacology
https://www.readbyqxmd.com/read/27571266/bile-acid-recognition-by-nape-pld
#19
Eleonora Margheritis, Beatrice Castellani, Paola Magotti, Sara Peruzzi, Elisa Romeo, Francesca Natali, Serena Mostarda, Antimo Gioiello, Daniele Piomelli, Gianpiero Garau
The membrane-associated enzyme NAPE-PLD (N-acyl phosphatidylethanolamine specific-phospholipase D) generates the endogenous cannabinoid arachidonylethanolamide and other lipid signaling amides, including oleoylethanolamide and palmitoylethanolamide. These bioactive molecules play important roles in several physiological pathways including stress and pain response, appetite, and lifespan. Recently, we reported the crystal structure of human NAPE-PLD and discovered specific binding sites for the bile acid deoxycholic acid...
October 21, 2016: ACS Chemical Biology
https://www.readbyqxmd.com/read/27566530/high-fat-diet-feeding-differentially-affects-the-development-of-inflammation-in-the-central-nervous-system
#20
Owein Guillemot-Legris, Julien Masquelier, Amandine Everard, Patrice D Cani, Mireille Alhouayek, Giulio G Muccioli
BACKGROUND: Obesity and its associated disorders are becoming a major health issue in many countries. The resulting low-grade inflammation not only affects the periphery but also the central nervous system. We set out to study, in a time-dependent manner, the effects of a high-fat diet on different regions of the central nervous system with regard to the inflammatory tone. METHODS: We used a diet-induced obesity model and compared at several time-points (1, 2, 4, 6, 8, and 16 weeks) a group of mice fed a high-fat diet with its respective control group fed a standard diet...
2016: Journal of Neuroinflammation
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