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Amides

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (31 August 2020) | Viewed by 35197

Special Issue Editors

Special Issue Information

Dear Colleagues,

We invite you to submit your valuable and latest research outcomes for publication in the Special Issue entitled “Amides” for the International Journal of Molecular SciencesIJMS (MDPI). The Special Issue will focus on the role and effectiveness of “Autacoid local injury antagonist amides” (ALIAmides) in health promotion and wellbeing.

ALIAmides are a family of endogenous bioactive acyl ethanolamides acting as bioregulators under inflammatory and oxidative stress conditions; their levels are principally regulated by enzymes responsible for their formation and degradation. N-palmitoylethanolamide (PEA) is considered to be the parent molecule of ALIAmides; it is known for its anti-inflammatory, analgesic and neuroprotective properties, and it exerts its anti-inflammatory effect by down-regulating mast-cell degranulation via an “Autacoid Local Inflammation Antagonism”(ALIA) effect. These endogenous bioactive lipids play a role in a number of biological processes, including pain, metabolism, and inflammation. The topic will include research studies on ALIAmides or their analogs, as plausible therapeutic strategies in the treatment of several inflammatory conditions such as chronic pain, tissue inflammation, chronic kidney disease, inflammatory bowel diseases, arthritis, osteoarthritis, and others.

Research articles collecting data from both in vitro and in vivo investigations are welcome.  Papers published in IJMS are encouraged to include results at molecular level. In addition, review articles reporting about the mode of actions of ALIAmides would complete the topic.

Dr. Daniela Impellizzeri
Dr. Rosalia Crupi
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

 

Keywords

  • Inflammation
  • ALIAmides
  • Pain
  • Oxidative stress
  • Mechanism of action
  • Molecular level

Published Papers (10 papers)

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Research

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25 pages, 3472 KiB  
Article
Synthesis, Molecular Modeling and Biological Evaluation of Metabolically Stable Analogues of the Endogenous Fatty Acid Amide Palmitoylethanolamide
by Alessia D’Aloia, Federica Arrigoni, Renata Tisi, Alessandro Palmioli, Michela Ceriani, Valentina Artusa, Cristina Airoldi, Giuseppe Zampella, Barbara Costa and Laura Cipolla
Int. J. Mol. Sci. 2020, 21(23), 9074; https://doi.org/10.3390/ijms21239074 - 28 Nov 2020
Cited by 1 | Viewed by 3176
Abstract
Palmitoylethanolamide (PEA) belongs to the class of N-acylethanolamine and is an endogenous lipid potentially useful in a wide range of therapeutic areas; products containing PEA are licensed for use in humans as a nutraceutical, a food supplement, or food for medical purposes [...] Read more.
Palmitoylethanolamide (PEA) belongs to the class of N-acylethanolamine and is an endogenous lipid potentially useful in a wide range of therapeutic areas; products containing PEA are licensed for use in humans as a nutraceutical, a food supplement, or food for medical purposes for its analgesic and anti-inflammatory properties demonstrating efficacy and tolerability. However, the exogenously administered PEA is rapidly inactivated; in this process, fatty acid amide hydrolase (FAAH) plays a key role both in hepatic metabolism and in intracellular degradation. So, the aim of the present study was the design and synthesis of PEA analogues that are more resistant to FAAH-mediated hydrolysis. A small library of PEA analogues was designed and tested by molecular docking and density functional theory calculations to find the more stable analogue. The computational investigation identified RePEA as the best candidate in terms of both synthetic accessibility and metabolic stability to FAAH-mediated hydrolysis. The selected compound was synthesized and assayed ex vivo to monitor FAAH-mediated hydrolysis and to confirm its anti-inflammatory properties. 1H-NMR spectroscopy performed on membrane samples containing FAAH in integral membrane protein demonstrated that RePEA is not processed by FAAH, in contrast with PEA. Moreover, RePEA retains PEA’s ability to inhibit LPS-induced cytokine release in both murine N9 microglial cells and human PMA-THP-1 cells. Full article
(This article belongs to the Special Issue Amides)
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22 pages, 9878 KiB  
Article
Protective Effects of Colomast®, a New Formulation of Adelmidrol and Sodium Hyaluronate, in a Mouse Model of Acute Restraint Stress
by Ramona D’Amico, Rosalba Siracusa, Roberta Fusco, Marika Cordaro, Tiziana Genovese, Alessio Filippo Peritore, Enrico Gugliandolo, Rosalia Crupi, Daniela Impellizzeri, Salvatore Cuzzocrea and Rosanna Di Paola
Int. J. Mol. Sci. 2020, 21(21), 8136; https://doi.org/10.3390/ijms21218136 - 30 Oct 2020
Cited by 16 | Viewed by 2294
Abstract
Stress is generally defined as a homeostatic disruption from actual or implied threats and alters the homeostatic balance of different body organs, such as gastrointestinal function and the hypothalamic-pituitary-adrenal axis (HPA), inducing the release of glucocorticoid hormones. Stress is also known to be [...] Read more.
Stress is generally defined as a homeostatic disruption from actual or implied threats and alters the homeostatic balance of different body organs, such as gastrointestinal function and the hypothalamic-pituitary-adrenal axis (HPA), inducing the release of glucocorticoid hormones. Stress is also known to be a risk factor for the development of depression and anxiety. However, until today there are no suitable therapies for treating of stress. The aim of this study was to explore the protective effect of Colomast®, a new preparation containing Adelmidrol, an enhancer of physiological of palmitoylethanolamide (PEA), and sodium hyaluronate in an animal model of immobilization stress. Acute restraint stress (ARS) was induced in mice by fixation for 2 h of the four extremities with an adhesive tape and Colomast® (20 mg/kg) was administered by oral gavage 30 min before the immobilization. Colomast® pre-treatment was able to decrease histopathological changes in the gastrointestinal tract, cytokines expression, neutrophil infiltration, mast cell activation, oxidative stress, as well as modulate nuclear factor NF-kB and apoptosis pathways after ARS induction. Moreover, Colomast® was able to restore tight junction in both ileum and hippocampus and cortex. Additionally, we demonstrated that Colomast® ameliorated depression and anxiety-related behaviours, and modulate inflammatory and apoptosis pathways also in brain after ARS induction. In conclusion, our results suggest Colomast® to be a potential approach to ARS. Full article
(This article belongs to the Special Issue Amides)
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13 pages, 3025 KiB  
Article
Synergic Therapeutic Potential of PEA-Um Treatment and NAAA Enzyme Silencing In the Management of Neuroinflammation
by Giovanna Casili, Marika Lanza, Michela Campolo, Rosalba Siracusa, Irene Paterniti, Alessio Ardizzone, Sarah Adriana Scuderi, Salvatore Cuzzocrea and Emanuela Esposito
Int. J. Mol. Sci. 2020, 21(20), 7486; https://doi.org/10.3390/ijms21207486 - 11 Oct 2020
Cited by 5 | Viewed by 2141
Abstract
Inflammation is a key element in the pathobiology of neurodegenerative diseases and sees the involvement of different neuronal and non-neuronal cells as players able to respond to inflammatory signals of immune origin. Palmitoylethanolamide (PEA) is an endogenous potent anti-inflammatory agent, in which activity [...] Read more.
Inflammation is a key element in the pathobiology of neurodegenerative diseases and sees the involvement of different neuronal and non-neuronal cells as players able to respond to inflammatory signals of immune origin. Palmitoylethanolamide (PEA) is an endogenous potent anti-inflammatory agent, in which activity is regulated by N-acylethanolamine acid amidase (NAAA), that hydrolyzes saturated or monounsaturated fatty acid ethanolamides, such as PEA. In this research, an in vitro study was performed on different neuronal (SH-SY5Y) and non-neuronal cell lines (C6, BV-2, and Mo3.13) subjected to NAAA enzyme silencing and treated with PEA ultra-micronized (PEA-um) (1, 3, and 10 μM) to increase the amount of endogenous PEA available for counteract neuroinflammation provoked by stimulation with lipopolysaccharide (LPS) (1 μg/mL) and interferon gamma (INF-γ )(100 U/mL). Cell viability was performed by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) staining, suggesting a protective effect of PEA-um (3 and 10 μM) on all cell lines studied. Western Blot analysis for inflammatory markers (Inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2)) was carried out in control and NAAA-silenced cells, highlighting how the concomitant treatment of the neuronal and non-neuronal cells with PEA-um after NAAA genic downregulation is satisfactory to counteract neuroinflammation. These in vitro findings support the protective role of endogenous PEA availability in the neuronal field, bringing interesting information for a translational point of view. Full article
(This article belongs to the Special Issue Amides)
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21 pages, 1783 KiB  
Article
Synthesis, Anticonvulsant and Antinociceptive Activity of New Hybrid Compounds: Derivatives of 3-(3-Methylthiophen-2-yl)-pyrrolidine-2,5-dione
by Małgorzata Góra, Anna Czopek, Anna Rapacz, Anna Dziubina, Monika Głuch-Lutwin, Barbara Mordyl and Jolanta Obniska
Int. J. Mol. Sci. 2020, 21(16), 5750; https://doi.org/10.3390/ijms21165750 - 11 Aug 2020
Cited by 15 | Viewed by 3328
Abstract
The present study aimed to design and synthesize a new series of hybrid compounds with pyrrolidine-2,5-dione and thiophene rings in the structure as potential anticonvulsant and antinociceptive agents. For this purpose, we obtained a series of new compounds and evaluated their anticonvulsant activity [...] Read more.
The present study aimed to design and synthesize a new series of hybrid compounds with pyrrolidine-2,5-dione and thiophene rings in the structure as potential anticonvulsant and antinociceptive agents. For this purpose, we obtained a series of new compounds and evaluated their anticonvulsant activity in animal models of epilepsy (maximal electroshock (MES), psychomotor (6 Hz), and subcutaneous pentylenetetrazole (scPTZ) seizure tests). To determine the mechanism of action of the most active anticonvulsant compounds (3, 4, 6, 9), their influence on the voltage-gated sodium and calcium channels as well as GABA transporter (GAT) was assessed. The most promising compound 3-(3-methylthiophen-2-yl)-1-(3-morpholinopropyl)pyrrolidine-2,5-dione hydrochloride (4) showed higher ED50 value than those of the reference drugs: valproic acid (VPA) and ethosuximide (ETX) (62.14 mg/kg vs. 252.7 mg/kg (VPA) in the MES test, and 75.59 mg/kg vs. 130.6 mg/kg (VPA) and 221.7 mg/kg (ETX) in the 6 Hz test, respectively). Moreover, in vitro studies of compound 4 showed moderate but balanced inhibition of the neuronal voltage-sensitive sodium (site 2) and L-type calcium channels. Additionally, the antinociceptive activity of the most active compounds (3, 4, 6, 9) was also evaluated in the hot plate test and writhing tests, and their hepatotoxic properties in HepG2 cells were also investigated. To determine the possible mechanism of the analgesic effect of compounds 3, 6, and 9, the affinity for the TRPV1 receptor was investigated. Full article
(This article belongs to the Special Issue Amides)
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23 pages, 3399 KiB  
Article
S(+)-(2E)-N-(2-Hydroxypropyl)-3-Phenylprop-2-Enamide (KM-568): A Novel Cinnamamide Derivative with Anticonvulsant Activity in Animal Models of Seizures and Epilepsy
by Agnieszka Gunia-Krzyżak, Ewa Żesławska, Karolina Słoczyńska, Dorota Żelaszczyk, Aleksandra Sowa, Paulina Koczurkiewicz-Adamczyk, Justyna Popiół, Wojciech Nitek, Elżbieta Pękala and Henryk Marona
Int. J. Mol. Sci. 2020, 21(12), 4372; https://doi.org/10.3390/ijms21124372 - 19 Jun 2020
Cited by 3 | Viewed by 2533
Abstract
Epilepsy is one of the most frequent neurological disorders affecting about 1% of the world’s human population. Despite availability of multiple treatment options including antiseizure drugs, it is estimated that about 30% of seizures still remain resistant to pharmacotherapy. Searching for new antiseizure [...] Read more.
Epilepsy is one of the most frequent neurological disorders affecting about 1% of the world’s human population. Despite availability of multiple treatment options including antiseizure drugs, it is estimated that about 30% of seizures still remain resistant to pharmacotherapy. Searching for new antiseizure and antiepileptic agents constitutes an important issue within modern medicinal chemistry. Cinnamamide derivatives were identified in preclinical as well as clinical studies as important drug candidates for the treatment of epilepsy. The cinnamamide derivative presented here: S(+)-(2E)-N-(2-hydroxypropyl)-3-phenylprop-2-enamide (S(+)-N-(2-hydroxypropyl)cinnamamide, compound KM-568) showed anticonvulsant activity in several models of epilepsy and seizures in mice and rats. It was active in a genetic animal model of epilepsy (Frings audiogenic seizure-susceptible mouse model, ED50 = 13.21 mg/kg, i.p.), acute seizures induced electrically (maximal electroshock test ED50 = 44.46 mg/kg mice i.p., ED50 = 86.6 mg/kg mice p.o., ED50 = 27.58 mg/kg rats i.p., ED50 = 30.81 mg/kg rats p.o., 6-Hz psychomotor seizure model 32 mA ED50 = 71.55 mg/kg mice i.p., 44 mA ED50 = 114.4 mg/kg mice i.p.), chronic seizures induced electrically (corneal kindled mouse model ED50 = 79.17 mg/kg i.p., hippocampal kindled rat model ED50 = 24.21 mg/kg i.p., lamotrigine-resistant amygdala kindled seizure model in rats ED50 = 58.59 mg/kg i.p.), acute seizures induced chemically (subcutaneous metrazol seizure threshold test ED50 = 104.29 mg/kg mice i.p., ED50 = 107.27 mg/kg mice p.o., ED50 = 41.72 mg/kg rats i.p., seizures induced by picrotoxin in mice ED50 = 94.11 mg/kg i.p.) and the pilocarpine-induced status epilepticus model in rats (ED50 = 279.45 mg/kg i.p., ED97 = 498.2 mg/kg i.p.). The chemical structure of the compound including configuration of the chiral center was confirmed by NMR spectroscopy, LC/MS spectroscopy, elemental analysis, and crystallography. Compound KM-568 was identified as a moderately stable derivative in an in vitro mouse liver microsome system. According to the Ames microplate format mutagenicity assay performed, KM-568 was not a base substitution or frameshift mutagen. Cytotoxicity evaluation in two cell lines (HepG2 and H9c2) proved the safety of the compound in concentrations up to 100 µM. Based on the results of anticonvulsant activity and safety profile, S(+)-(2E)-N-(2-hydroxypropyl)-3-phenylprop-2-enamide could be proposed as a new lead compound for further preclinical studies on novel treatment options for epilepsy. Full article
(This article belongs to the Special Issue Amides)
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17 pages, 12315 KiB  
Article
Looking for a Treatment for the Early Stage of Alzheimer’s Disease: Preclinical Evidence with Co-Ultramicronized Palmitoylethanolamide and Luteolin
by Roberta Facchinetti, Marta Valenza, Maria Rosanna Bronzuoli, Giorgia Menegoni, Patrizia Ratano, Luca Steardo, Patrizia Campolongo and Caterina Scuderi
Int. J. Mol. Sci. 2020, 21(11), 3802; https://doi.org/10.3390/ijms21113802 - 27 May 2020
Cited by 21 | Viewed by 2827
Abstract
Background: At the earliest stage of Alzheimer’s disease (AD), although patients are still asymptomatic, cerebral alterations have already been triggered. In addition to beta amyloid (Aβ) accumulation, both glial alterations and neuroinflammation have been documented at this stage. Starting treatment at this prodromal [...] Read more.
Background: At the earliest stage of Alzheimer’s disease (AD), although patients are still asymptomatic, cerebral alterations have already been triggered. In addition to beta amyloid (Aβ) accumulation, both glial alterations and neuroinflammation have been documented at this stage. Starting treatment at this prodromal AD stage could be a valuable therapeutic strategy. AD requires long-term care; therefore, only compounds with a high safety profile can be used, such as the new formulation containing palmitoylethanolamide and luteolin (co-ultra PEALut) already approved for human use. Therefore, we investigated it in an in vivo pharmacological study that focused on the prodromal stage of AD. Methods: We tested the anti-inflammatory and neuroprotective effects of co-ultra PEALut (5 mg/Kg) administered for 14 days in rats that received once, 5 µg Aβ(1–42) into the hippocampus. Results: Glial activation and elevated levels of proinflammatory mediators were observed in Aβ-infused rats. Early administration of co-ultra PEALut prevented the Aβ-induced astrogliosis and microgliosis, the upregulation in gene expression of pro-inflammatory cytokines and enzymes, as well as the reduction of mRNA levels BDNF and GDNF. Our findings also highlight an important neuroprotective effect of co-ultra PEALut treatment, which promoted neuronal survival. Conclusions: Our results reveal the presence of cellular and molecular modifications in the prodromal stage of AD. Moreover, the data presented here demonstrate the ability of co-ultra PEALut to normalize such Aβ-induced alterations, suggesting it as a valuable therapeutic strategy. Full article
(This article belongs to the Special Issue Amides)
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17 pages, 2504 KiB  
Article
Ultramicronized Palmitoylethanolamide and Paracetamol, a New Association to Relieve Hyperalgesia and Pain in a Sciatic Nerve Injury Model in Rat
by Alessio Filippo Peritore, Rosalba Siracusa, Roberta Fusco, Enrico Gugliandolo, Ramona D’Amico, Marika Cordaro, Rosalia Crupi, Tiziana Genovese, Daniela Impellizzeri, Salvatore Cuzzocrea and Rosanna Di Paola
Int. J. Mol. Sci. 2020, 21(10), 3509; https://doi.org/10.3390/ijms21103509 - 15 May 2020
Cited by 47 | Viewed by 3241
Abstract
Inflammation is known to be an essential trigger of the pathological changes that have a critical impact on nerve repair and regeneration; moreover, damage to peripheral nerves can cause a loss of sensory function and produces persistent neuropathic pain. To date, various potential [...] Read more.
Inflammation is known to be an essential trigger of the pathological changes that have a critical impact on nerve repair and regeneration; moreover, damage to peripheral nerves can cause a loss of sensory function and produces persistent neuropathic pain. To date, various potential approaches for neuropathic pain have focused on controlling neuroinflammation. The aim of this study was to investigate the neuroprotective effects of a new association of ultramicronized Palmitoylethanolamide (PEAum), an Autacoid Local Injury Antagonist Amide (ALIAmide) with analgesic and anti-inflammatory properties, with Paracetamol, a common analgesic, in a rat model of sciatic nerve injury (SNI). The association of PEAum–Paracetamol, in a low dose (5 mg/kg + 30 mg/kg), was given by oral gavage daily for 14 days after SNI. PEAum–Paracetamol association was able to reduce hyperalgesia, mast cell activation, c-Fos and nerve growth factor (NGF) expression, neural histological damage, cytokine release, and apoptosis. Furthermore, the analgesic action of PEAum–Paracetamol could act in a synergistic manner through the inhibition of the NF-κB pathway, which leads to a decrease of cyclooxygenase 2-dependent prostaglandin E2 (COX-2/PGE2) release. In conclusion, we demonstrated that PEAum associated with Paracetamol was able to relieve pain and neuroinflammation after SNI in a synergistic manner, and this therapeutic approach could be relevant to decrease the demand of analgesic drugs. Full article
(This article belongs to the Special Issue Amides)
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Review

Jump to: Research

12 pages, 723 KiB  
Review
Prebiotic Organic Chemistry of Formamide and the Origin of Life in Planetary Conditions: What We Know and What Is the Future
by Bruno Mattia Bizzarri, Raffaele Saladino, Ines Delfino, Juan Manuel García-Ruiz and Ernesto Di Mauro
Int. J. Mol. Sci. 2021, 22(2), 917; https://doi.org/10.3390/ijms22020917 - 18 Jan 2021
Cited by 14 | Viewed by 3797
Abstract
The goal of prebiotic chemistry is the depiction of molecular evolution events preceding the emergence of life on Earth or elsewhere in the cosmos. Plausible experimental models require geochemical scenarios and robust chemistry. Today we know that the chemical and physical conditions for [...] Read more.
The goal of prebiotic chemistry is the depiction of molecular evolution events preceding the emergence of life on Earth or elsewhere in the cosmos. Plausible experimental models require geochemical scenarios and robust chemistry. Today we know that the chemical and physical conditions for life to flourish on Earth were at work much earlier than thought, i.e., earlier than 4.4 billion years ago. In recent years, a geochemical model for the first five hundred million years of the history of our planet has been devised that would work as a cradle for life. Serpentinization processes in the Hadean eon affording self-assembled structures and vesicles provides the link between the catalytic properties of the inorganic environment and the impressive chemical potential of formamide to produce complete panels of organic molecules relevant in pre-genetic and pre-metabolic processes. Based on an interdisciplinary approach, we propose basic transformations connecting geochemistry to the chemistry of formamide, and we hint at the possible extension of this perspective to other worlds. Full article
(This article belongs to the Special Issue Amides)
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25 pages, 744 KiB  
Review
Palmitoylethanolamide: A Nutritional Approach to Keep Neuroinflammation within Physiological Boundaries—A Systematic Review
by Stefania Petrosino and Aniello Schiano Moriello
Int. J. Mol. Sci. 2020, 21(24), 9526; https://doi.org/10.3390/ijms21249526 - 15 Dec 2020
Cited by 25 | Viewed by 5938
Abstract
Neuroinflammation is a physiological response aimed at maintaining the homodynamic balance and providing the body with the fundamental resource of adaptation to endogenous and exogenous stimuli. Although the response is initiated with protective purposes, the effect may be detrimental when not regulated. The [...] Read more.
Neuroinflammation is a physiological response aimed at maintaining the homodynamic balance and providing the body with the fundamental resource of adaptation to endogenous and exogenous stimuli. Although the response is initiated with protective purposes, the effect may be detrimental when not regulated. The physiological control of neuroinflammation is mainly achieved via regulatory mechanisms performed by particular cells of the immune system intimately associated with or within the nervous system and named “non-neuronal cells.” In particular, mast cells (within the central nervous system and in the periphery) and microglia (at spinal and supraspinal level) are involved in this control, through a close functional relationship between them and neurons (either centrally, spinal, or peripherally located). Accordingly, neuroinflammation becomes a worsening factor in many disorders whenever the non-neuronal cell supervision is inadequate. It has been shown that the regulation of non-neuronal cells—and therefore the control of neuroinflammation—depends on the local “on demand” synthesis of the endogenous lipid amide Palmitoylethanolamide and related endocannabinoids. When the balance between synthesis and degradation of this bioactive lipid mediator is disrupted in favor of reduced synthesis and/or increased degradation, the behavior of non-neuronal cells may not be appropriately regulated and neuroinflammation exceeds the physiological boundaries. In these conditions, it has been demonstrated that the increase of endogenous Palmitoylethanolamide—either by decreasing its degradation or exogenous administration—is able to keep neuroinflammation within its physiological limits. In this review the large number of studies on the benefits derived from oral administration of micronized and highly bioavailable forms of Palmitoylethanolamide is discussed, with special reference to neuroinflammatory disorders. Full article
(This article belongs to the Special Issue Amides)
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27 pages, 1012 KiB  
Review
ALIAmides Update: Palmitoylethanolamide and Its Formulations on Management of Peripheral Neuropathic Pain
by Ramona D’Amico, Daniela Impellizzeri, Salvatore Cuzzocrea and Rosanna Di Paola
Int. J. Mol. Sci. 2020, 21(15), 5330; https://doi.org/10.3390/ijms21155330 - 27 Jul 2020
Cited by 37 | Viewed by 5234
Abstract
Neuropathic pain results from lesions or diseases of the somatosensory nervous system and it remains largely difficult to treat. Peripheral neuropathic pain originates from injury to the peripheral nervous system (PNS) and manifests as a series of symptoms and complications, including allodynia and [...] Read more.
Neuropathic pain results from lesions or diseases of the somatosensory nervous system and it remains largely difficult to treat. Peripheral neuropathic pain originates from injury to the peripheral nervous system (PNS) and manifests as a series of symptoms and complications, including allodynia and hyperalgesia. The aim of this review is to discuss a novel approach on neuropathic pain management, which is based on the knowledge of processes that underlie the development of peripheral neuropathic pain; in particular highlights the role of glia and mast cells in pain and neuroinflammation. ALIAmides (autacoid local injury antagonist amides) represent a group of endogenous bioactive lipids, including palmitoylethanolamide (PEA), which play a central role in numerous biological processes, including pain, inflammation, and lipid metabolism. These compounds are emerging thanks to their anti-inflammatory and anti-hyperalgesic effects, due to the down-regulation of activation of mast cells. Collectively, preclinical and clinical studies support the idea that ALIAmides merit further consideration as therapeutic approach for controlling inflammatory responses, pain, and related peripheral neuropathic pain. Full article
(This article belongs to the Special Issue Amides)
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