Mauro Maccarrone

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Verified

Mauro verified their affiliation via an institutional email.

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• MS, PhD, FRSC
• Professor & Chair at University of L'Aquila

[This corrects the article DOI: 10.1155/2014/169203.].

Pharmacological modulation of cannabinoid type 2 receptor (CB2R) holds promise for the treatment of numerous con-ditions, including inflammatory diseases, autoimmune disorders, pain, and cancer. Despite the significance of this re-ceptor, researchers lack reliable tools to address questions concerning the expression and complex mechanism of CB2R si...

Little information is available concerning the structural features of nucleotide pyrophosphatase/phosphodiesterases (NPPs) of plant origin and the crystal structures of these proteins have not yet been reported. The aim of this study was to obtain insight into these aspects by carrying out a comparative analysis of the sequences of two different fr...

Increased circulating sclerostin and accumulation of advanced glycation end‐products (AGEs) are two potential mechanisms underlying low bone turnover and increased fracture risk in type 2 diabetes (T2D). Whether the expression of the sclerostin‐encoding SOST gene is altered in T2D, and whether it is associated with AGEs accumulation or regulation o...

Background DNA methylation plays a relevant role in the regulation of gene transcription, but currently the exact quantification of transcription factors binding to methylated DNA is not being determined. The binding of the transcription factor cAMP response element-binding protein-1 to its cognate CpG containing motif is known to be impaired upon...

Endogenous bioactive lipids are part of a complex network that modulates a plethora of cellular and molecular processes involved in health and disease, of which inflammation represents one of the most prominent examples. Inflammation serves as a well-conserved defence mechanism, triggered in the event of chemical, mechanical or microbial damage, th...

Since the first Apollo mission in 1969, microgravity has been linked to many alterations of astronauts’ physiology, among which immunosuppression, altered inflammation and bone loss represent relevant examples. In the past 40 years, extensive investigations have been conducted in order to characterize the molecular mechanisms driving the alteration...

Pharmacological modulation of cannabinoid type 2 receptor (CB₂R) holds promise for the treatment of numerous conditions, including inflammatory diseases, autoimmune disorders, pain, and cancer. Despite the significance of this receptor, researchers lack reliable tools to address questions concerning the expression and complex mechanism o...

[This corrects the article DOI: 10.1155/2018/3591086.].

In the context of Space Medicine, the aim of “SERiSM” (Role of the Endocannabinoid System in Reprogramming human pluripotent Stem cells under Microgravity) project, selected by the Italian Space Agency, was to study the involvement of the endocannabinoid system (ECS) in the osteogenic differentiation under real microgravity. An innovative and easil...

Amniotic epithelial cells (AEC) have been proposed as promising clinical candidates for regenerative medicine therapies due to their immunomodulatory capacity. In this context, the endocannabinoid system (ECS) has been identified as mediating the immune-stem cell dialogue, even if no information on AEC is available to date. Therefore, this study wa...

Introduction: Fatty acid amide hydrolase (FAAH) is a membrane-bound enzyme, that inactivates endogenous signaling lipids of the fatty acid amide family, including the endocannabinoid anandamide (N-arachidonoylethanolamine, AEA). The latter compound has been shown to regulate a number of important pathophysiological conditions in humans, like feedin...

Objective Both environmental and genetic factors are known to contribute to the development of anorexia nervosa (AN), but the exact etiology remains poorly understood. Herein, we studied the transcriptional regulation of the endocannabinoid system, an interesting target for body weight maintenance and the control of food intake and energy balance....

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Background: Endocannabinoids (ECs) modulate both excitatory and inhibitory components in the CNS. There is a growing body of evidence that shows ECs influence both hypothalamic orexinergic and histaminergic neurons involved in narcolepsy physiopathology. Therefore, ECs may influence sleep and sleep-wake cycle. Objective: To evaluate EC levels in...

Background: Social Anxiety Disorder (SAD) is a relatively frequent psychiatric disorder, with a lifetime prevalence of about 4% [1], which usually starts in adolescence [2]. As in the case of other mental disorders, [3] SAD has also been linked to academic impairment and school drop-out [4,5], but this previous research has a number of methodologic...

Fatty acid amide hydrolase (FAAH) is a membrane-bound homodimeric enzyme that in vivo controls content and biological activity of N-arachidonoylethanolamine (AEA) and other relevant bioactive lipids termed endocannabinoids. Parallel orientation of FAAH monomers likely allows both subunits to simultaneously recruit and cleave substrates. Here, we sh...

Background: The concentrations of three N-acylethanolamines (NAEs), anandamide (AEA), N-oleoylethanolamide (OEA), and N-palmitylethanolamide (PEA) are increased in the endometria of women with endometrial cancer (EC). It is widely accepted that plasma levels of these three NAEs are regulated by the actions of the rate-limiting enzymes N-acylphoshat...

[This corrects the article DOI: 10.1155/2019/8107265.].

The most bioactive ingredient of cannabis (Cannabis sativa or indica) extracts, Δ9-tetrahydrocannabinol (THC), was identified in the 1960s as one of more than 110 phytocannabinoids. It activates receptors of chemically different endogenous ligands (endocannabinoids) that, unlike THC, are metabolized by several enzymes of the endocannabinoid system....

Cannabis extracts like marijuana have the highest consumption rate worldwide. Yet, their societal acceptance as recreational and therapeutic drugs could represent a serious hazard to female human reproduction, because cannabis ingredients [termed (phyto)cannabinoids] can perturb an endogenous system of lipid signals known as endocannabinoids. Accum...

Pharmacological modulation of cannabinoid type 2 receptor (CB2R) holds promise for the treatment of numerous conditions including inflammatory diseases, autoimmune disorders, pain, and cancer. Despite its significance, researchers lack reliable tools to address questions concerning the complex mechanism of CB2R signaling and its downstream conseque...

Cannabinoid type 2 receptor (CB₂R) is a fundamental part of the endocannabinoid signaling system (eCB system), and is known to play an important role in tissue injury, inflammation, cancer and pain. In stark contrast to its significance, the underlying signaling mechanisms and tissue expression profiles are poorly understood. Due to its...

Cannabinoid type 2 receptor (CB 2 R) is a fundamental part of the endocannabinoid signaling system (eCB system), and is known to play an important role in tissue injury, inflammation, cancer and pain. In stark contrast to its significance, the underlying signaling mechanisms and tissue expression profiles are poorly understood. Due to its low expre...

Pharmacological modulation of cannabinoid type 2 receptor (CB2R) holds promise for the treatment of numerous conditions including inflammatory diseases, autoimmune disorders, pain, and cancer. Despite its significance, researchers lack reliable tools to address questions concerning the complex mechanism of CB2R signaling and its downstream conseque...

We investigated the cellular and molecular mechanisms by which bindarit, a small indazolic derivative with prominent anti-inflammatory effects, exerts its immunoregulatory activity in lipopolysaccharide (LPS) stimulated human monocytic cells. We found that bindarit differentially regulates the release of interleukin-8 (IL-8) and monocyte chemoattra...

Objective: To determine if plasma concentrations of the N-acylethanolamines (NAEs) N-arachidonoylethanolamine (AEA), N-oleoylethanolamide (OEA) and N-palmitoylethanolamide (PEA) increase in women at high risk for preterm birth (PTB) and whether these could be used to predict preterm delivery and if so, how they compare with current methods. Desig...

ABHD2 is a serine hydrolase that belongs to the subgroup of the α,β-hydrolase fold containing proteins, which is involved in virus propagation, immune response and fertilization. Chemical tools to selectively modulate the activity of ABHD2 in an acute setting are highly desired to investigate its biological role, but are currently lacking. Here, we...

There is robust evidence indicating that enhancing the endocannabinoid (eCB) tone has therapeutic potential in several brain disorders. The inhibition of eCBs degradation by fatty acid amide hydrolase (FAAH) blockade, is the best-known option to increase N-acyl-ethanolamines-(NAEs)-mediated signaling. Here, we investigated the hypothesis that intra...

Polypharmacology approaches may help the discovery of pharmacological tools for the study or the potential treatment of complex and multifactorial diseases as well as for addictions and also smoke cessation. In this frame, following our interest in the development of molecules able to modulate either the endocannabi-noid or the dopaminergic system,...

In the present work, mice overexpressing mutant amyloid precursor protein (Tg2576), a transgenic model of Alzheimer's disease (AD), are used to investigate a specific lipid profile over the course of disease progression. Using a targeted lipidomic approach, plasma levels of N ‐acylethanolamines with different length and unsaturation at presymptomat...

5-lipoxygenase (5-LOX) is a non-heme iron-containing dioxygenase expressed in immune cells that catalyzes the two initial steps in the biosynthesis of leukotrienes. It is well known that 5-LOX activation in innate immunity cells is related to different iron-associated pro-inflammatory disorders, including cancer, neurodegenerative diseases, and ath...

Specialized proresolving mediators (SPMs) are a novel class of endogenous lipids, derived by ω -6 and ω -3 essential polyunsaturated fatty acids such as arachidonic acid (AA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA) that trigger and orchestrate the resolution of inflammation, which is the series of cellular and molecular events...

Among endogenous signaling networks involved in both rewarding and homeostatic mechanisms of obesity, a relevant role is played by the endocannabinoid (ECS) and the opioid (EOS) systems. We here studied the transcriptional regulation of ECS and EOS genes in the hypothalamus of Diet-induced obesity rats, a preclinical model of obesity, as well as in...

Endocannabinoids are key-players of female fertility and potential biomarkers of reproductive dysfunctions. Here, we investigated localization and expression of cannabinoid receptor type-1 and -2 (CB1R and CB2R), G-protein coupled receptor 55 (GPR55), and transient receptor potential vanilloid type 1 channel (TRPV1) in mouse oocytes collected at di...

Objective: To identify new biochemical markers for endometrial cancer (EC). Recent evidence suggests that members of the endocannabinoid system (N-acylethanolamines) that bind to and activate receptors that are dysregulated in EC are involved in this tumour's biology. These observations suggest increased N-acylethanolamine levels in the tissue that...

In the frame of the VITA mission of the Italian Space Agency (ASI), we addressed the problem of Space osteoporosis by using human blood-derived stem cells (BDSCs) as a suitable osteogenic differentiation model. In particular, we investigated proteomic and epigenetic changes in BDSCs during osteoblastic differentiation induced by rapamycin under mic...

Background: Pharmacological treatment approaches for eating disorders, such as binge eating disorder and bulimia nervosa, are currently limited. Methods and aims: Using a well-characterized animal model of binge eating, we investigated the epigenetic regulation of the A2A Adenosine Receptor (A2AAR) and dopaminergic D2 receptor (D2R) genes. Resu...

Fragility fractures are major complications in type 2 diabetes (T2D), but mechanisms underlying bone fragility are still poorly clarified. Bone mineral density (BMD) underestimates T2D fracture incidence, since a normal or even higher BMD is associated with a greater fracture risk than healthy population. We hypothesized that bone fragility in T2D...

In the past two decades, there has been an increasing interest in the therapeutic potential of cannabinoids for neurological disorders such as epilepsy, multiple sclerosis, pain, and neurodegenerative diseases. Cannabis-based treatments for pain and spasticity in patients with multiple sclerosis have been approved in some countries. Randomised cont...

Endocannabinoid (eCB)-binding receptors can be modulated by several ligands and membrane environment, yet the effect of glycosylation remains to be assessed. In this study, we used human neuroblastoma SH-SY5Y cells to interrogate whether expression, cellular localization, and activity of eCB-binding receptors may depend on N-linked glycosylation. F...

Obsessive-compulsive disorder (OCD) is a clinically heterogeneous neuropsychiatric condition associated with profound disability, whose susceptibility, stemming from genetic and environmental factors that intersect with each other, is still under investigation. In this perspective, we sought to explore the transcriptional regulation of Brain Derive...

Background: Fatty acid amide hydrolase (FAAH) is a membrane-bound homodimeric enzyme that gets in contact with a lipophilic substrate in the lipid bilayer, and then cleaves it into water soluble products. FAAH plays a critical role in modulating in vivo content and biological activity of endocannabinoids (eCBs), and its function is affected by memb...

Objective Binge‐eating episodes are recurrent and are defining features of several eating disorders. Thus binge‐eating episodes might influence eating disorder development of which exact underlying mechanisms are still largely unknown. Methods Here we focused on the transcriptional regulation of the endocannabinoid system, a potent regulator of fe...

Growing evidence suggests that endocannabinoid levels are modulated during pathological conditions affecting both central and peripheral nervous system. In the present study, a novel approach (patent pending) based on an innovative liquid biosensor has been used to analyze two relevant endocannabinoid molecules with calibration purposes: N-arachido...

The relationship between varicocele and fertility has always been a matter of debate because of the absence of predictive clinical indicators or molecular markers able to define the severity of this disease. Even though accumulated evidence demonstrated that the endocannabinoid system (ECS) plays a central role in male reproductive biology, particu...

In agreement with the neurodevelopmental hypothesis of schizophrenia, prenatal exposure of rats to the antimitotic agent methylazoxymethanol acetate (MAM) at gestational day 17 produced long-lasting behavioral alterations such as social withdrawal and cognitive impairment in the social interaction test and in the novel object recognition test, resp...

Objective: Systemic lupus erythematosus (SLE) is an autoimmune systemic disease and its pathogenesis has not yet been completely clarified. Patients with SLE show a deranged lipid metabolism, which can contribute to the immunopathogenesis of the disease and to the accelerated atherosclerosis. Resolvin D1 (RvD1), a product of the metabolism of the...

Chronic heart failure (CHF) is characterized by an ongoing nonresolving inflammatory status, where T lymphocytes seem critical. It has been recently recognized that transition from acute to chronic inflammation could be caused by defects in resolving inflammation, the resolution of which is mediated by a novel family of ω‐3‐derived specialized pror...

Alcohol exposure and stressful events in life can induce long-lasting changes in physiology, behavior and gene expression patterns, eventually facilitating the development of psychiatric diseases like alcohol use disorders (AUD). Epigenetic mechanisms have been recently proposed to play a role in the cellular actions of alcohol via chromatin remode...

Autacoid local injury antagonist amides (ALIAmides) are a family of endogenous bioactive acyl ethanolamides that include the renowned palmitoyl ethanolamide (PEA), oleoyl ethanolamide (OEA), and stearoyl ethanolamide (SEA), and that are involved in several biologic processes such as nociception, lipid metabolism and inflammation. The role of ALIAmi...

Background: Experiencing traumatic childhood is a risk factor for developing substance use disorder, but the mechanisms that underlie this relationship have not been determined. Adverse childhood experiences affect the immune system, and the immune system mediates the effects of psychostimulants. However, whether this system is involved in the eti...

2-Arachidonoylglycerol (2-AG) is a signaling lipid in the central nervous system that is a key regulator of neurotransmitter release. 2-AG is an endocannabinoid that activates the cannabinoid CB1 receptor. It is involved in a wide array of (patho)physiological functions, such as emotion, cognition, energy balance, pain sensation and neuroinflammati...

Palatable food can be seductive and hedonic eating can become irresistible beyond hunger and negative consequences. This is witnessed by the subtle equilibrium between eating to provide energy intake for homeostatic functions, and reward-induced overeating. In recent years, considerable efforts have been devoted to study neural circuits, and to ide...

The endocannabinoid (eCB) system plays a key role in many physiological and pathological conditions and its dysregulation has been described in several rheumatological and autoimmune diseases. Yet, its possible alteration in systemic lupus erythematosus (SLE) has never been investigated. Here, we aimed filling this gap in plasma and peripheral bloo...

In view of the need for easily accessible biomarkers, we evaluated in ADHD children the epigenetic status of the 5'-untranslated region (UTR) in the SLC6A3 gene, coding for human dopamine transporter (DAT). We analysed buccal swabs and sera from 30 children who met DSM-IV-TR criteria for ADHD, assigned to treatment according to severity. Methylatio...

Besides its involvement in Alzheimer's disease (AD) as precursor of the neurotoxic amyloid peptides, the pathophysiological impact of brain accumulation of amyloid precursor protein (APP) is not yet well understood. Recent studies reported that APP interacts with other membrane proteins, including G protein coupled receptors, affecting their biolog...

Inflammation is an immune response that works as a contained fire that is pre-emptively sparked as a defensive process during infections or upon any kind of tissue insult, and that is spontaneously extinguished after elimination or termination of the damage. However, persistent and uncontrolled immune reactions act as a wildfire that promote chroni...

Multiple sclerosis is the most common inflammatory demyelinating disease of the central nervous system, caused by an autoimmune response against myelin that eventually leads to progressive neurodegeneration and disability. Although the knowledge on its underlying neurobiological mechanisms has considerably improved, there is a still unmet need for...

The endocannabinoid system (ECS) is nowadays considered as an important neurotransmitter system and, although the chemistry, biochemistry and pharmacology of endocannabinoids (eCBs) have been widely investigated, quite some pieces are still missing to fully understand how this system works. The discovery of anandamide (AEA) and 2‐arachidonoylglycer...

This minireview focuses on a plant copper/TPQ amine oxidase isolated from the latex of the shrub Euphorbia characias (ELAO). This enzyme has been investigated in terms of both molecular structure and kinetic mechanism. The characterization of this enzyme allowed us to identify specific amino acids and domains that play a key role in modulating subs...

Lipoxygenases (LOXs) are non-heme iron containing enzymes catalyzing the dioxygenation of polyunsaturated fatty acids. LOX catalytic activity depends on the presence of iron in the active site and the iron removal is also able to affect the membrane binding properties of the enzyme. Leukotrienes biosynthesis is initiated by the action of 5-LOX at t...

The recent resolution of the crystal structure of type-1 cannabinoid receptor (CB1), and the discovery of novel modulators for this target open the way to the possibility of elucidating the structural requirements for CB1 binding, and thereby facilitate a rational drug design. Compounds that target the orthosteric site of CB1 in some cases have sho...

Bipolar Disorder (BD) is a prevalent and disabling condition, determined by gene-environment interactions, possibly mediated by epigenetic mechanisms. The present study aimed at investigating the transcriptional regulation of BD selected target genes by DNA methylation in peripheral blood mononuclear cells of patients with a DSM-5 diagnosis of type...

Background: Emerging neuroprotective strategies are being explored to preserve the retina from degeneration, that occurs in eye pathologies like glaucoma, diabetic retinopathy, age-related macular degeneration, and retinitis pigmentosa. Incidentally, neuroprotection of retina is a defending mechanism designed to prevent or delay neuronal cell deat...

In this study, we investigated the role of CB1 palmitoylation in modulating the functional interaction with G proteins both in the absence and in the presence of agonist binding. Our data show that the non-palmitoylated CB1 receptor significantly reduced its association with Gαi2 . The agonist-stimulation induced a partial dissociation of Gαi2 prot...

Polyphenols-rich cocoa has many beneficial effects on human health, such as anti-inflammatory effects. Macrophages function as control switches of the immune system, maintaining the balance between pro- and anti-inflammatory activities. We investigated the hypothesis that cocoa polyphenol extract may affect macrophage proinflammatory phenotype M1 b...

Significance: Under physiological conditions, neurons and glia are in a healthy, redox-balanced environment; when injury perturbs this equilibrium, a neuroinflammatory state is established by activated microglia that triggers pro-inflammatory responses and alters the oxidant/antioxidant balance, thus leading to neuronal loss and neurodegeneration....

A clue to a drug's neurotoxicity? The drug BIA 10-2474 inhibits fatty acid amide hydrolase (FAAH), a lipase that degrades a specific endocannabinoid. On the basis of this activity, BIA 10-2474 was being developed as a potential treatment for anxiety and pain. In a phase 1 trial of the drug, one subject died, and four others suffered brain damage. A...

Cannabis extracts have been used for centuries, but its main active principle ∆⁹-tetrahydrocannabinol (THC) was identified about 50 years ago. Yet, it is only 25 years ago that the first endogenous ligand of the same receptors engaged by the cannabis agents was discovered. This “endocannabinoid (eCB)” was identified as N-arachidonoylethanolamine (o...

Twenty-five years after the discovery of the first cannabinoid receptor, several efforts have been made to identify the biochemical routes potentially used by cells to produce its endogenous ligands anandamide and 2-arachidonoylglycerol. These endocannabinoids (eCBs) are key molecules engaged in multiple biological processes that, together with the...

The capsaicin receptor TRPV1 has been widely characterized in the sensory system as a key component of pain and inflammation. A large amount of evidence shows that TRPV1 is also functional in the brain although its role is still debated. Here we report that TRPV1 is highly expressed in microglial cells rather than neurons of the anterior cingulate...

Supplementary Figures and Supplementary References.

The first day included five oral sessions on the following subjects: (1) Medicinal Cannabis I, that featured six presentations and was chaired by Dr. Dror Robinson (HaSharon Hospital of Petah Tikwa, Israel) and Dr. Mark A. Ware (McGill University of Montreal, Canada); the latter also delivered the inaugural talk on “Pharmacovigilance of medical can...

Introduction: The complexity of the endocannabinoid (eCB) system is becoming better understood and new drivers of eCB signaling are emerging. Modulation of the activities of the eCB system can be therapeutic in a number of diseases. Research into the eCB system has been paralleled by the development of agents that interact with cannabinoid recepto...

PurposeThe etiology of maternal aging, a common cause of female factor infertility and a rate-limiting step in vitro fertilization (IVF) success, remains still unclear. Proteomic changes responsible for the impaired successful pregnancy outcome after IVF with aged blastocysts have not been yet evaluated. The objective of this prospective study was...

We previously demonstrated that CB1 receptor is palmitoylated at cysteine 415, and that such a post-translational modification affects its biological activity. To assess the molecular mechanisms responsible for modulation of CB1 receptor function by S-palmitoylation, in this study biochemical and morphological approaches were paralleled with comput...

Compelling evidence supports the involvement of the endocannabinoid system (ECS) in psychosis vulnerability. We here evaluated the transcriptional regulation of ECS components in human peripheral blood mononuclear cells (PBMCs) obtained from subjects suffering from bipolar disorder, major depressive disorder and schizophrenia, focusing in particula...

By means of functional genomics analysis, we recently described the mRNA expression profiles of various genes involved in the neuroinflammatory response in the brains of subjects with late-onset Alzheimer Disease (LOAD). Some of these genes, namely interleukin (IL)-1β and IL-6, showed distinct expression profiles with peak expression during the fir...