To Go Where Nature Leads: Focus on Palmitoylethanolamide and Related ALIAmides As Innovative Approach to Neuroinflammatory and Pain-Related Disease States in Honor of Doctor Francesco Della Valle

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Biological Factors".

Deadline for manuscript submissions: closed (10 December 2022) | Viewed by 37286

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editors


E-Mail Website
Guest Editor
Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy
Interests: physiopatology of ischemia and reperfusion (myocardium, intestine, brain); physiopathology of Spinal Cord Injury; physiophatology of Alzheimer and Parkinson Diseases; physiopathology of acute and chronic infiammatory processes in: rheumatoid arthritis, pulmonary fibrosis, pleurisy, colitis; neuroinflammatory and neurodegenerative diseases; endocannabinoids and natural substances

E-Mail Website
Guest Editor
Department of Veterinary Science, University of Messina, 98168 Messina, Italy
Interests: veterinary pharmacology and toxicology; preclinical and clinical studies of inflammatory and neuroinflamma-tory diseases; endocannabinoids and natural substances, as antioxidant and anti-inflammatory; to improve an-imal health and welfare
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We are pleased to invite you to contribute to this Special Issue entitled “To go where nature leads: focus on Palmitoylethanolamide and related ALIAmides as innovative approach to neuroinflammatory and pain-related disease states in honor of Doctor Francesco della Valle”. Palmitoylethanolamide (PEA) is an endocannabinoid-like lipid mediator and the parent molecule of ALIAmides (i.e., Autacoid Local Injury Antagonist amides). As with other naturally occurring ALIAmides and related endocannabinoids, PEA is naturally synthesized “on demand” in response to actual or potential injuries and serves as an early stop signal to counteract inflammation. Its action depends on multiple molecular targets belonging to the endocannabinoidome. In the last few decades, a growing body of evidence has shown that the regulation of non-neuronal cells—and, therefore, the control of neuroinflammation—depends, at least in part, on the local synthesis of PEA and related endocannabinoids. This mechanism plays important roles in protection against human and animal chronic disorders, ranging from Alzheimer’s disease to enteropathies and from neuropathic pain to allergic dermatitis and itch, to name just a few. Since local and circulating levels of PEA have been repeatedly shown to severely decrease in several conditions, one might envision that the body’s own PEA production is not always fully sufficient. The use of PEA and related ALIAmides, as well as the manipulation of their endogenous levels ,may thus serve as plausible “according-to-Nature” strategies in the management of chronic neuroinflammatory conditions. This Special Issue aims to bring together cutting-edge articles on PEA and related ALIAmides in different in vitro or in vivo disease models and clinical settings in areas of neuroinflammatory and pain-related disorders. We hope this Special Issue can provide a platform for both researchers and practitioners to exchange the latest results on this challenging biopharmaceutics field. We invite you to contribute original research, review articles, or short communications, and we look forward to receiving your contributions.

Prof. Dr. Salvatore Cuzzocrea
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. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). 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

  • palmitoylethanolamide
  • ALIAmides
  • neuroinflammation
  • pain

Published Papers (14 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Editorial

Jump to: Research, Review

2 pages, 184 KiB  
Editorial
To Go Where Nature Leads: Focus on Palmitoylethanolamide and Related ALIAmides as Innovative Approach to Neuroinflammatory and Pain-Related Disease States in Honor of Doctor Francesco Della Valle
by Salvatore Cuzzocrea and Rosalia Crupi
Biomolecules 2023, 13(11), 1583; https://doi.org/10.3390/biom13111583 - 26 Oct 2023
Viewed by 1103

Research

Jump to: Editorial, Review

21 pages, 4197 KiB  
Article
Ultramicronized N-Palmitoylethanolamine Regulates Mast Cell-Astrocyte Crosstalk: A New Potential Mechanism Underlying the Inhibition of Morphine Tolerance
by Alessandra Toti, Laura Micheli, Elena Lucarini, Valentina Ferrara, Clara Ciampi, Francesco Margiotta, Paola Failli, Chiara Gomiero, Marco Pallecchi, Gianluca Bartolucci, Carla Ghelardini and Lorenzo Di Cesare Mannelli
Biomolecules 2023, 13(2), 233; https://doi.org/10.3390/biom13020233 - 25 Jan 2023
Cited by 1 | Viewed by 1641
Abstract
Persistent pain can be managed with opioids, but their use is limited by the onset of tolerance. Ultramicronized N-palmitoylethanolamine (PEA) in vivo delays morphine tolerance with mechanisms that are still unclear. Since glial cells are involved in opioid tolerance and mast cells [...] Read more.
Persistent pain can be managed with opioids, but their use is limited by the onset of tolerance. Ultramicronized N-palmitoylethanolamine (PEA) in vivo delays morphine tolerance with mechanisms that are still unclear. Since glial cells are involved in opioid tolerance and mast cells (MCs) are pivotal targets of PEA, we hypothesized that a potential mechanism by which PEA delays opioid tolerance might depend on the control of the crosstalk between these cells. Morphine treatment (30 μM, 30 min) significantly increased MC degranulation of RBL-2H3 cells, which was prevented by pre-treatment with PEA (100 μM, 18 h), as evaluated by β-hexosaminidase assay and histamine quantification. The impact of RBL-2H3 secretome on glial cells was studied. Six-hour incubation of astrocytes with control RBL-2H3-conditioned medium, and even more so co-incubation with morphine, enhanced CCL2, IL-1β, IL-6, Serpina3n, EAAT2 and GFAP mRNA levels. The response was significantly prevented by the secretome from PEA pre-treated RBL-2H3, except for GFAP, which was further upregulated, suggesting a selective modulation of glial signaling. In conclusion, ultramicronized PEA down-modulated both morphine-induced MC degranulation and the expression of inflammatory and pain-related genes from astrocytes challenged with RBL-2H3 medium, suggesting that PEA may delay morphine tolerance, regulating MC-astrocyte crosstalk. Full article
Show Figures

Figure 1

12 pages, 2201 KiB  
Article
First Evidence of the Protective Effects of 2-Pentadecyl-2-Oxazoline (PEA-OXA) in In Vitro Models of Acute Lung Injury
by Aniello Schiano Moriello, Fiorentina Roviezzo, Fabio Arturo Iannotti, Giuseppina Rea, Marco Allarà, Rosa Camerlingo, Roberta Verde, Vincenzo Di Marzo and Stefania Petrosino
Biomolecules 2023, 13(1), 33; https://doi.org/10.3390/biom13010033 - 24 Dec 2022
Cited by 3 | Viewed by 1424
Abstract
Acute respiratory distress syndrome (ARDS) is a serious inflammatory lung disorder and a complication of SARS-CoV-2 infection. In patients with severe SARS-CoV-2 infection, the transition to ARDS is principally due to the occurrence of a cytokine storm and an exacerbated inflammatory response. The [...] Read more.
Acute respiratory distress syndrome (ARDS) is a serious inflammatory lung disorder and a complication of SARS-CoV-2 infection. In patients with severe SARS-CoV-2 infection, the transition to ARDS is principally due to the occurrence of a cytokine storm and an exacerbated inflammatory response. The effectiveness of ultra-micronized palmitoylethanolamide (PEA-um) during the earliest stage of COVID-19 has already been suggested. In this study, we evaluated its protective effects as well as the effectiveness of its congener, 2-pentadecyl-2-oxazoline (PEA-OXA), using in vitro models of acute lung injury. In detail, human lung epithelial cells (A549) activated by polyinosinic–polycytidylic acid (poly-(I:C)) or Transforming Growth Factor-beta (TGF-β) were treated with PEA-OXA or PEA. The release of IL-6 and the appearance of Epithelial–Mesenchymal Transition (EMT) were measured by ELISA and immunofluorescence assays, respectively. A possible mechanism of action for PEA-OXA and PEA was also investigated. Our results showed that both PEA-OXA and PEA were able to counteract poly-(I:C)-induced IL-6 release, as well as to revert TGF-β-induced EMT. In addition, PEA was able to produce an “entourage” effect on the levels of the two endocannabinoids AEA and 2-AG, while PEA-OXA only increased PEA endogenous levels, in poly-(I:C)-stimulated A549 cells. These results evidence for the first time the superiority of PEA-OXA over PEA in exerting protective effects and point to PEA-OXA as a new promising candidate in the management of acute lung injury. Full article
Show Figures

Figure 1

18 pages, 3145 KiB  
Article
Palmitoylethanolamide Mitigates Paclitaxel Toxicity in Primary Dorsal Root Ganglion Neurons
by Amira Elfarnawany and Faramarz Dehghani
Biomolecules 2022, 12(12), 1873; https://doi.org/10.3390/biom12121873 - 14 Dec 2022
Cited by 4 | Viewed by 2469
Abstract
Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of several chemotherapeutic agents, such as Paclitaxel. The main symptoms of CIPN are pain and numbness in the hands and feet. Paclitaxel is believed to accumulate in the dorsal root ganglia and free nerve [...] Read more.
Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of several chemotherapeutic agents, such as Paclitaxel. The main symptoms of CIPN are pain and numbness in the hands and feet. Paclitaxel is believed to accumulate in the dorsal root ganglia and free nerve endings. Novel therapeutic agents might help to mitigate or prevent Paclitaxel toxicity on dorsal root ganglion (DRG) neurons. Thus, we used primary DRG neurons as a model to investigate the potential neuroprotective effects of the endocannabinoid-like substance, palmitoylethanolamide (PEA). DRG neurons were isolated from cervical to sacral segments of spinal nerves of Wister rats (6–8 weeks old). After isolation and purification of neuronal cell populations, different concentrations of Paclitaxel (0.01–10 µM) or PEA (0.1–10 µM) or their combination were tested on cell viability by MTT assay at 24 h, 48, and 72 h post-treatment. Furthermore, morphometric analyses of neurite length and soma size for DRG neurons were performed. Adverse Paclitaxel effects on cell viability were apparent at 72 h post-treatment whereas Paclitaxel significantly reduced the neurite length in a concentration-dependent manner nearly at all investigated time points. However, Paclitaxel significantly increased the size of neuronal cell bodies at all time windows. These phenotypic effects were significantly reduced in neurons additionally treated with PEA, indicating the neuroprotective effect of PEA. PEA alone led to a significant increase in neuron viability regardless of PEA concentrations, apparent improvements in neurite outgrowth as well as a significant decrease in soma size of neurons at different investigated time points. Taken together, PEA showed promising protective effects against Paclitaxel-related toxicity on DRG neurons. Full article
Show Figures

Figure 1

14 pages, 6692 KiB  
Article
Aerosol-Administered Adelmidrol Attenuates Lung Inflammation in a Murine Model of Acute Lung Injury
by Livia Interdonato, Ramona D’amico, Marika Cordaro, Rosalba Siracusa, Roberta Fusco, Alessio Filippo Peritore, Enrico Gugliandolo, Rosalia Crupi, Stefano Coaccioli, Tiziana Genovese, Daniela Impellizzeri, Rosanna Di Paola and Salvatore Cuzzocrea
Biomolecules 2022, 12(9), 1308; https://doi.org/10.3390/biom12091308 - 16 Sep 2022
Cited by 7 | Viewed by 1981
Abstract
Acute lung injury (ALI) is a common and devastating clinical disorder with a high mortality rate and no specific therapy. The pathophysiology of ALI is characterized by increased alveolar/capillary permeability, lung inflammation, oxidative stress and structural damage to lung tissues, which can progress [...] Read more.
Acute lung injury (ALI) is a common and devastating clinical disorder with a high mortality rate and no specific therapy. The pathophysiology of ALI is characterized by increased alveolar/capillary permeability, lung inflammation, oxidative stress and structural damage to lung tissues, which can progress to acute respiratory distress syndrome (ARDS). Adelmidrol (ADM), an analogue of palmitoylethanolamide (PEA), is known for its anti-inflammatory and antioxidant functions, which are mainly due to down-modulating mast cells (MCs) and promoting endogenous antioxidant defense. The aim of this study is to evaluate the protective effects of ADM in a mice model of ALI, induced by intratracheal administration of lipopolysaccharide (LPS) at the dose of 5 mg/kg. ADM 2% was administered by aerosol 1 and 6 h after LPS instillation. In this study, we clearly demonstrated that ADM reduced lung damage and airway infiltration induced by LPS instillation. At the same time, ADM counteracted the increase in MC number and the expression of specific markers of MC activation, i.e., chymase and tryptase. Moreover, ADM reduced oxidative stress by upregulating antioxidant enzymes as well as modulating the Nf-kB pathway and the resulting pro-inflammatory cytokine release. These results suggest that ADM could be a potential candidate in the management of ALI. Full article
Show Figures

Figure 1

13 pages, 2283 KiB  
Article
N-Palmitoyl-D-Glucosamine Inhibits TLR-4/NLRP3 and Improves DNBS-Induced Colon Inflammation through a PPAR-α-Dependent Mechanism
by Irene Palenca, Luisa Seguella, Alessandro Del Re, Silvia Basili Franzin, Chiara Corpetti, Marcella Pesce, Sara Rurgo, Luca Steardo, Giovanni Sarnelli and Giuseppe Esposito
Biomolecules 2022, 12(8), 1163; https://doi.org/10.3390/biom12081163 - 22 Aug 2022
Cited by 10 | Viewed by 2463
Abstract
Similar to canine inflammatory enteropathy, inflammatory bowel disease (IBD) is a chronic idiopathic condition characterized by remission periods and recurrent flares in which diarrhea, visceral pain, rectal bleeding/bloody stools, and weight loss are the main clinical symptoms. Intestinal barrier function alterations often persist [...] Read more.
Similar to canine inflammatory enteropathy, inflammatory bowel disease (IBD) is a chronic idiopathic condition characterized by remission periods and recurrent flares in which diarrhea, visceral pain, rectal bleeding/bloody stools, and weight loss are the main clinical symptoms. Intestinal barrier function alterations often persist in the remission phase of the disease without ongoing inflammatory processes. However, current therapies include mainly anti-inflammatory compounds that fail to promote functional symptoms-free disease remission, urging new drug discoveries to handle patients during this step of the disease. ALIAmides (ALIA, autacoid local injury antagonism) are bioactive fatty acid amides that recently gained attention because of their involvement in the control of inflammatory response, prompting the use of these molecules as plausible therapeutic strategies in the treatment of several chronic inflammatory conditions. N-palmitoyl-D-glucosamine (PGA), an under-researched ALIAmide, resulted in being safe and effective in preclinical models of inflammation and pain, suggesting its potential engagement in the treatment of IBD. In our study, we demonstrated that micronized PGA significantly and dose-dependently reduces colitis severity, improves intestinal mucosa integrity by increasing the tight junction proteins expression, and downregulates the TLR-4/NLRP3/iNOS pathway via PPAR-α receptors signaling in DNBS-treated mice. The possibility of clinically exploiting micronized PGA as support for the treatment and prevention of inflammation-related changes in IBD patients would represent an innovative, effective, and safe strategy. Full article
Show Figures

Figure 1

16 pages, 1995 KiB  
Article
The Beneficial Effects of Ultramicronized Palmitoylethanolamide in the Management of Neuropathic Pain and Associated Mood Disorders Induced by Paclitaxel in Mice
by Claudia Cristiano, Carmen Avagliano, Mariarosaria Cuozzo, Fabrizio Maria Liguori, Antonio Calignano and Roberto Russo
Biomolecules 2022, 12(8), 1155; https://doi.org/10.3390/biom12081155 - 20 Aug 2022
Cited by 8 | Viewed by 2371
Abstract
Chemotherapy-induced peripheral neuropathy (CIPN) is a common complication of antineoplastic drugs, particularly paclitaxel (PTX). It can affect the quality of patients’ lives and increase the risk of developing mood disorders. Although several drugs are recommended, they yielded inconclusive results in clinical trials. The [...] Read more.
Chemotherapy-induced peripheral neuropathy (CIPN) is a common complication of antineoplastic drugs, particularly paclitaxel (PTX). It can affect the quality of patients’ lives and increase the risk of developing mood disorders. Although several drugs are recommended, they yielded inconclusive results in clinical trials. The aim of the present work is to investigate whether the palmitoylethanolamide (PEA) would reduce PTX-induced CIPN and associated mood disorders. Moreover, the role PPAR-α and the endocannabinoid system will also be investigated. CIPN was induced by intraperitoneally injection of PTX (8 mg/kg) every other day for a week. PEA, 30 mg/kg, was orally administrated in a bioavailable form (i.e., ultramicronized PEA, um-PEA) one hour after the last PTX injection, for 7 days. In the antagonism experiments, AM281 (1 mg/kg) and GW6471 (2 mg/kg) were administrated 30 min before um-PEA. Our results demonstrated that um-PEA reduced the development of hypersensitivity with the effect being associated with the reduction in spinal and hippocampal pro-inflammatory cytokines, as well as antidepressive and anxiolytic effects. Moreover, the PPAR-α and CB1 receptor antagonists blocked the behavioral and antinociceptive effects of um-PEA. Our findings suggest that um-PEA is a promising adjunct in CIPN and associated mood disorders through the activation of PPAR-α, which influences the endocannabinoid system. Full article
Show Figures

Graphical abstract

Review

Jump to: Editorial, Research

13 pages, 1595 KiB  
Review
Targeting Neuroinflammation in Osteoarthritis with Intra-Articular Adelmidrol
by Francesca Guida, Monica Rocco, Livio Luongo, Pietro Persiani, Maria Chiara Vulpiani, Sveva Maria Nusca, Sabatino Maione and Flaminia Coluzzi
Biomolecules 2022, 12(10), 1453; https://doi.org/10.3390/biom12101453 - 11 Oct 2022
Cited by 5 | Viewed by 2315
Abstract
Neuroinflammation is an emerging therapeutic target in chronic degenerative and autoimmune diseases, such as osteoarthritis (OA) and rheumatoid arthritis. Mast cells (MCs) play a key role in the homeostasis of joints and the activation of MCs induces the release of a huge number [...] Read more.
Neuroinflammation is an emerging therapeutic target in chronic degenerative and autoimmune diseases, such as osteoarthritis (OA) and rheumatoid arthritis. Mast cells (MCs) play a key role in the homeostasis of joints and the activation of MCs induces the release of a huge number of mediators, which fuel the fire of neuroinflammation. Particularly, synovial MCs release substances which accelerate the degradation of the extra-cellular matrix causing morphological joint changes and cartilage damage and inducing the proliferation of synovial fibroblasts, angiogenesis, and the sprouting of sensory nerve fibers, which mediate chronic pain. Palmitoylethanolamide (PEA) is a well-known MCs modulator, but in osteoarthritic joints, its levels are significantly reduced. Adelmidrol, a synthetic derivate of azelaic acid belonging to the ALIAmides family, is a PEA enhancer. Preclinical and clinical investigations showed that the intra-articular administration of Adelmidrol significantly reduced MC infiltration, pro-inflammatory cytokine release, and cartilage degeneration. The combination of 1% high molecular weight hyaluronic acid and 2% Adelmidrol has been effectively used for knee osteoarthritis and, a significant improvement in analgesia and functionality has been recorded. Full article
Show Figures

Figure 1

15 pages, 1471 KiB  
Review
Palmitoylethanolamide and White Matter Lesions: Evidence for Therapeutic Implications
by Marta Valenza, Roberta Facchinetti, Luca Steardo and Caterina Scuderi
Biomolecules 2022, 12(9), 1191; https://doi.org/10.3390/biom12091191 - 27 Aug 2022
Cited by 3 | Viewed by 2935
Abstract
Palmitoylethanolamide (PEA), the naturally occurring amide of ethanolamine and palmitic acid, is an endogenous lipid compound endowed with a plethora of pharmacological functions, including analgesic, neuroprotective, immune-modulating, and anti-inflammatory effects. Although the properties of PEA were first characterized nearly 65 years ago, the [...] Read more.
Palmitoylethanolamide (PEA), the naturally occurring amide of ethanolamine and palmitic acid, is an endogenous lipid compound endowed with a plethora of pharmacological functions, including analgesic, neuroprotective, immune-modulating, and anti-inflammatory effects. Although the properties of PEA were first characterized nearly 65 years ago, the identity of the receptor mediating these actions has long remained elusive, causing a period of research stasis. In the last two decades, a renewal of interest in PEA occurred, and a series of interesting studies have demonstrated the pharmacological properties of PEA and clarified its mechanisms of action. Recent findings showed the ability of formulations containing PEA in promoting oligodendrocyte differentiation, which represents the first step for the proper formation of myelin. This evidence opens new and promising research opportunities. White matter defects have been detected in a vast and heterogeneous group of diseases, including age-related neurodegenerative disorders. Here, we summarize the history and pharmacology of PEA and discuss its therapeutic potential in restoring white matter defects. Full article
Show Figures

Figure 1

14 pages, 1609 KiB  
Review
Palmitoylethanolamide and Related ALIAmides for Small Animal Health: State of the Art
by Giorgia della Rocca and Giovanni Re
Biomolecules 2022, 12(9), 1186; https://doi.org/10.3390/biom12091186 - 26 Aug 2022
Cited by 3 | Viewed by 2635
Abstract
ALIAmides are a family of fatty acid amides whose name comes from their mechanism of action, i.e., the Autacoid Local Injury Antagonism (ALIA). Actually, the ALIAmide parent molecule, palmitoylethanolamide (PEA), is locally produced on demand from a cell membrane precursor in order to [...] Read more.
ALIAmides are a family of fatty acid amides whose name comes from their mechanism of action, i.e., the Autacoid Local Injury Antagonism (ALIA). Actually, the ALIAmide parent molecule, palmitoylethanolamide (PEA), is locally produced on demand from a cell membrane precursor in order to control immune-inflammatory cell responses, avert chronic non-resolving inflammation, and limit the resulting clinical signs. ALIAmide sister compounds, such as Adelmidrol and palmitoylglucosamine, share mechanisms of action with PEA and may also increase endogenous levels of PEA. Provided that their respective bioavailability is properly addressed (e.g., through decreasing the particle size through micronization), exogenously administered ALIAmides thus mimic or sustain the prohomeostatic functions of endogenous PEA. The aim of the present paper is to review the main findings on the use of ALIAmides in small animals as a tribute to the man of vision who first believed in this “according-to-nature” approach, namely Francesco della Valle. After briefly presenting some key issues on the molecular targets, metabolism, and pharmacokinetics of PEA and related ALIAmides, here we will focus on the preclinical and clinical studies performed in dogs and cats. Although more data are still needed, ALIAmides may represent a novel and promising approach to small animal health. Full article
Show Figures

Figure 1

16 pages, 1196 KiB  
Review
Synaptic Effects of Palmitoylethanolamide in Neurodegenerative Disorders
by Martina Assogna, Francesco Di Lorenzo, Alessandro Martorana and Giacomo Koch
Biomolecules 2022, 12(8), 1161; https://doi.org/10.3390/biom12081161 - 22 Aug 2022
Cited by 9 | Viewed by 3019
Abstract
Increasing evidence strongly supports the key role of neuroinflammation in the pathophysiology of neurodegenerative diseases, such as Alzheimer’s disease, frontotemporal dementia, and amyotrophic lateral sclerosis. Neuroinflammation may alter synaptic transmission contributing to the progression of neurodegeneration, as largely documented in animal models and [...] Read more.
Increasing evidence strongly supports the key role of neuroinflammation in the pathophysiology of neurodegenerative diseases, such as Alzheimer’s disease, frontotemporal dementia, and amyotrophic lateral sclerosis. Neuroinflammation may alter synaptic transmission contributing to the progression of neurodegeneration, as largely documented in animal models and in patients’ studies. In the last few years, palmitoylethanolamide (PEA), an endogenous lipid mediator, and its new composite, which is a formulation constituted of PEA and the well-recognized antioxidant flavonoid luteolin (Lut) subjected to an ultra-micronization process (co-ultraPEALut), has been identified as a potential therapeutic agent in different disorders by exerting potential beneficial effects on neurodegeneration and neuroinflammation by modulating synaptic transmission. In this review, we will show the potential therapeutic effects of PEA in animal models and in patients affected by neurodegenerative disorders. Full article
Show Figures

Figure 1

11 pages, 303 KiB  
Review
Classical and Unexpected Effects of Ultra-Micronized PEA in Neuromuscular Function
by Pierangelo Cifelli, Gabriele Ruffolo, Marco Ceccanti, Chiara Cambieri, Laura Libonati, Eleonora Palma and Maurizio Inghilleri
Biomolecules 2022, 12(6), 758; https://doi.org/10.3390/biom12060758 - 29 May 2022
Cited by 1 | Viewed by 2119
Abstract
Recently, the endocannabinoid system has attracted growing attention from the scientific community for its involvement in homeostatic and pathological processes as they pertains to human physiology. Among the constituents of the endocannabinoid system, the molecule palmitoyl ethanolamide has particularly been studied for its [...] Read more.
Recently, the endocannabinoid system has attracted growing attention from the scientific community for its involvement in homeostatic and pathological processes as they pertains to human physiology. Among the constituents of the endocannabinoid system, the molecule palmitoyl ethanolamide has particularly been studied for its ability to reduce several inflammatory processes involving the central nervous system. Here, we reviewed published literature and summarized the main targets of the palmitoyl ethanolamide, along with its unique possible mechanisms for restoring correct functioning of the central nervous system. Moreover, we have highlighted a less-known characteristic of palmitoyl ethanolamide, namely its ability to modulate the function of the neuromuscular junction by binding to acetylcholine receptors in different experimental conditions. Indeed, there are several studies that have highlighted how ultra-micronized palmitoyl ethanolamide is an interesting nutraceutical support for the treatment of pathological neuromuscular conditions, specifically when the normal activity of the acetylcholine receptor is altered. Although further multicentric clinical trials are needed to confirm the efficacy of ultra-micronized palmitoyl ethanolamide in improving symptoms of neuromuscular diseases, all the literature reviewed here strongly supports the ability of this endocannabinoid-like molecule to modulate the acetylcholine receptors thus resulting as a valid support for the treatment of human neuromuscular diseases. Full article
17 pages, 604 KiB  
Review
Effects of Palmitoylethanolamide on Neurodegenerative Diseases: A Review from Rodents to Humans
by Eugenia Landolfo, Debora Cutuli, Laura Petrosini and Carlo Caltagirone
Biomolecules 2022, 12(5), 667; https://doi.org/10.3390/biom12050667 - 05 May 2022
Cited by 11 | Viewed by 4494
Abstract
Palmitoylethanolamide (PEA) stands out among endogenous lipid mediators for its neuroprotective, anti-inflammatory, and analgesic functions. PEA belonging to the N-acetylanolamine class of phospholipids was first isolated from soy lecithin, egg yolk, and peanut flour. It is currently used for the treatment of different [...] Read more.
Palmitoylethanolamide (PEA) stands out among endogenous lipid mediators for its neuroprotective, anti-inflammatory, and analgesic functions. PEA belonging to the N-acetylanolamine class of phospholipids was first isolated from soy lecithin, egg yolk, and peanut flour. It is currently used for the treatment of different types of neuropathic pain, such as fibromyalgia, osteoarthritis, carpal tunnel syndrome, and many other conditions. The properties of PEA, especially of its micronized or ultra-micronized forms maximizing bioavailability and efficacy, have sparked a series of innovative research to evaluate its possible application as therapeutic agent for neurodegenerative diseases. Neurodegenerative diseases are widespread throughout the world, and although they are numerous and different, they share common patterns of conditions that result from progressive damage to the brain areas involved in mobility, muscle coordination and strength, mood, and cognition. The present review is aimed at illustrating in vitro and in vivo research, as well as human studies, using PEA treatment, alone or in combination with other compounds, in the presence of neurodegeneration. Namely, attention has been paid to the effects of PEA in counteracting neuroinflammatory conditions and in slowing down the progression of diseases, such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, Frontotemporal dementia, Amyotrophic Lateral Sclerosis, and Multiple Sclerosis. Literature research demonstrated the efficacy of PEA in addressing the damage typical of major neurodegenerative diseases. Full article
Show Figures

Figure 1

14 pages, 968 KiB  
Review
Role of EPA in Inflammation: Mechanisms, Effects, and Clinical Relevance
by Rosalia Crupi and Salvatore Cuzzocrea
Biomolecules 2022, 12(2), 242; https://doi.org/10.3390/biom12020242 - 01 Feb 2022
Cited by 20 | Viewed by 4419
Abstract
Many chronic inflammatory processes are linked with the continuous release of inflammatory mediators and the activation of harmful signal-transduction pathways that are able to facilitate disease progression. In this context atherosclerosis represents the most common pathological substrate of coronary heart disease, and the [...] Read more.
Many chronic inflammatory processes are linked with the continuous release of inflammatory mediators and the activation of harmful signal-transduction pathways that are able to facilitate disease progression. In this context atherosclerosis represents the most common pathological substrate of coronary heart disease, and the characterization of the disease as a chronic low-grade inflammatory condition is now validated. The biomarkers of inflammation associated with clinical cardiovascular risk support the theory that targeted anti-inflammatory treatment appears to be a promising strategy in reducing residual cardiovascular risk. Several literature data highlight cardioprotective effects of the long-chain omega-3 polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (EPA). This PUFA lowers plasma triglyceride levels and has potential beneficial effects on atherosclerotic plaques. Preclinical studies reported that EPA reduces both pro-inflammatory cytokines and chemokines levels. Clinical studies in patients with coronary artery disease that receive pharmacological statin therapy suggest that EPA may decrease plaque vulnerability preventing plaque progression. This review aims to provide an overview of the links between inflammation and cardiovascular risk factors, importantly focusing on the role of diet, in particular examining the proposed role of EPA as well as the success or failure of standard pharmacological therapy for cardiovascular diseases. Full article
Show Figures

Figure 1

Back to TopTop