The endocannabinoid system and its therapeutic exploitation in multiple sclerosis: Clues for other neuroinflammatory diseases DOI Creative Commons
Valerio Chiurchiù, Mario van der Stelt, Diego Centonze

и другие.

Progress in Neurobiology, Год журнала: 2017, Номер 160, С. 82 - 100

Опубликована: Окт. 31, 2017

Multiple sclerosis is the most common inflammatory demyelinating disease of central nervous system, caused by an autoimmune response against myelin that eventually leads to progressive neurodegeneration and disability. Although knowledge on its underlying neurobiological mechanisms has considerably improved, there a still unmet need for new treatment options, especially forms disease. Both preclinical clinical data suggest cannabinoids, derived from Cannabis sativa plant, may be used control symptoms such as spasticity chronic pain, whereas only indicate these compounds their endogenous counterparts, i.e. endocannabinoids, also exert neuroprotective effects slow down progression. Here, we review studies could explain therapeutic action cannabinoid-based medicines, well medical potential modulating endocannabinoid signaling in multiple sclerosis, with link other neuroinflammatory disorders share hallmarks pathogenetic features.

Язык: Английский

Cannabinoid Receptors and the Endocannabinoid System: Signaling and Function in the Central Nervous System DOI Open Access

Shenglong Zou,

Ujendra Kumar

International Journal of Molecular Sciences, Год журнала: 2018, Номер 19(3), С. 833 - 833

Опубликована: Март 13, 2018

The biological effects of cannabinoids, the major constituents ancient medicinal plant Cannabis sativa (marijuana) are mediated by two members G-protein coupled receptor family, cannabinoid receptors 1 (CB1R) and 2. CB1R is prominent subtype in central nervous system (CNS) has drawn great attention as a potential therapeutic avenue several pathological conditions, including neuropsychological disorders neurodegenerative diseases. Furthermore, cannabinoids also modulate signal transduction pathways exert profound at peripheral sites. Although have potential, their psychoactive largely limited use clinical practice. In this review, we briefly summarized our knowledge endocannabinoid system, focusing on CNS, with emphasis recent breakthroughs field. We aim to define roles modulation signaling association pathophysiological conditions. believe that significance masked adverse here alternative strategies discussed take advantage cannabinoids.

Язык: Английский

Процитировано

1135

The endocannabinoid system in guarding against fear, anxiety and stress DOI
Beat Lutz, Giovanni Marsicano, Rafaël Maldonado

и другие.

Nature reviews. Neuroscience, Год журнала: 2015, Номер 16(12), С. 705 - 718

Опубликована: Ноя. 20, 2015

Язык: Английский

Процитировано

431

Bioactive Lipids and Chronic Inflammation: Managing the Fire Within DOI Creative Commons
Valerio Chiurchiù, Alessandro Leuti, Mauro Maccarrone

и другие.

Frontiers in Immunology, Год журнала: 2018, Номер 9

Опубликована: Янв. 29, 2018

Inflammation is an immune response that works as a contained fire pre-emptively sparked defensive process during infections or upon any kind of tissue insult, and spontaneously extinguished after elimination termination the damage. However, persistent uncontrolled reactions act wildfire promote chronic inflammation, unresolved damage and, eventually, diseases. A wide network soluble mediators, among which endogenous bioactive lipids, governs all processes. They are secreted by basically cells involved in inflammatory processes constitute crucial infrastructure trigger, coordinate confine mechanisms. these molecules also deeply detrimental transition from to be it for excessive action pro-inflammatory lipids impairment functions carried out resolving ones. As matter fact, have been linked, date, several diseases, including rheumatoid arthritis, atherosclerosis, diabetes, cancer, bowel disease, lupus multiple sclerosis. This review summarizes current knowledge on involvement main classes – namely classical eicosanoids, pro-resolving lipid lysoglycerophospholipids/sphingolipids endocannabinoids cellular molecular mechanisms lead pathogenesis disorders.

Язык: Английский

Процитировано

379

Anti-Inflammatory Effects of Omega-3 Fatty Acids in the Brain: Physiological Mechanisms and Relevance to Pharmacology DOI Open Access
Sophie Layé, Agnès Nadjar, Corinne Joffre

и другие.

Pharmacological Reviews, Год журнала: 2017, Номер 70(1), С. 12 - 38

Опубликована: Дек. 7, 2017

Classically, polyunsaturated fatty acids (PUFA) were largely thought to be relatively inert structural components of brain, important for the formation cellular membranes. Over past 10 years, a host bioactive lipid mediators that are enzymatically derived from arachidonic acid, main n-6 PUFA, and docosahexaenoic n-3 PUFA in known regulate peripheral immune function, have been detected brain shown microglia activation. Recent advances focused on how molecular signaling microglia, especially context neuroinflammation behavior. Several active drugs provide proof concept targeting brain. Because metabolism relies complex integration diet, metabolism, including liver blood, which supply with PUFAs can altered by genetics, sex, aging, there many pathways disrupted, leading homeostasis. Brain neurologic disorders may viable targets development novel therapeutics. In this study, we discuss particular their metabolites phenotype function exert anti-inflammatory proresolving activities

Язык: Английский

Процитировано

353

Endocannabinoids — at the crossroads between the gut microbiota and host metabolism DOI
Patrice D. Cani, Hubert Plovier, Matthias Van Hul

и другие.

Nature Reviews Endocrinology, Год журнала: 2015, Номер 12(3), С. 133 - 143

Опубликована: Дек. 18, 2015

Язык: Английский

Процитировано

316

Cannabinoid Receptors in the Central Nervous System: Their Signaling and Roles in Disease DOI Creative Commons
Debra A. Kendall, Guillermo A. Yudowski

Frontiers in Cellular Neuroscience, Год журнала: 2017, Номер 10

Опубликована: Янв. 3, 2017

The identification and cloning of the two major cannabinoid (CB¬1 CB2) receptors together with discovery their endogenous ligands in late 80s early 90s, resulted a effort aimed at understanding mechanisms physiological roles endocannabinoid system (ECS). Due to its expression localization central nervous (CNS), CB1 receptor (endocannabinoids) enzymes involved synthesis degradation, has been implicated multiple pathophysiological events ranging from memory deficits neurodegenerative disorders among others. In this review, we will provide general overview emphasis on health disease. We describe our current complex aspects signaling trafficking, including non-canonical pathways such as those mediated by β-arrestins within context functional selectivity ligand bias. Finally, highlight some which have implicated. Significant knowledge achieved over last 30 years. However, much more research is still needed fully understand system, particularly vivo, unlock true potential source therapeutic targets.

Язык: Английский

Процитировано

305

Comprehensive review of mechanisms of pathogenesis involved in Alzheimer’s disease and potential therapeutic strategies DOI
Piyoosh Sharma,

Pavan Srivastava,

Ankit Seth

и другие.

Progress in Neurobiology, Год журнала: 2018, Номер 174, С. 53 - 89

Опубликована: Дек. 30, 2018

Язык: Английский

Процитировано

286

Cannabinoids and Cytochrome P450 Interactions DOI
Ondřej Zendulka,

Gabriela Dovrtělová,

Kristýna Nosková

и другие.

Current Drug Metabolism, Год журнала: 2016, Номер 17(3), С. 206 - 226

Опубликована: Янв. 21, 2016

This review consists of three parts, representing different possibilities interactions between cannabinoid receptor ligands both exogenous and endogenous origin cytochrome P450 enzymes (CYPs). The first part deals with cannabinoids as CYP substrates, the second summarizes current knowledge on influence various metabolic activity CYP, third outline a possible involvement endocannabinoid system in regulation liver activity.We performed structured search bibliographic drug databases for peer-reviewed literature using focused questions.Biotransformation via hydrolytic pathway is major route metabolism deactivation substrates characteristic, contrast to minor oxidative involved bioactivation reactions. Phytocannabinoids are extensively metabolized by CYPs. CYP2C9, CYP2C19, CYP3A4 catalyze most their hydroxylations. Similarly, represents synthetic used therapeutically drugs that abused. In vitro experiments document mostly inhibitory phytocannabinoids, cannabidiol potent inhibitor many drug-drug at level reported, but clinical relevance remains unclear. direct activation/inhibition nuclear receptors cells may result change expression activity. Finally, we hypothesize interplay central numerous nervous systems, resulting hormone-mediated signal towards hepatocytes.

Язык: Английский

Процитировано

247

Bioactive lipids, inflammation and chronic diseases DOI
Alessandro Leuti, Domenico Fazio, Marina Fava

и другие.

Advanced Drug Delivery Reviews, Год журнала: 2020, Номер 159, С. 133 - 169

Опубликована: Янв. 1, 2020

Язык: Английский

Процитировано

245

A chronic low dose of Δ9-tetrahydrocannabinol (THC) restores cognitive function in old mice DOI
András Bilkei‐Gorzó, Önder Albayram,

Astrid M. Draffehn

и другие.

Nature Medicine, Год журнала: 2017, Номер 23(6), С. 782 - 787

Опубликована: Май 8, 2017

Язык: Английский

Процитировано

219