Targeting Endocannabinoid Metabolism: an Arrow with Multiple Tips Against Multiple Sclerosis

Multiple sclerosis (MS) is a chronic, immune‐mediated disease of the central nervous system. At present, there is no definitive cure, and the few available disease‐modifying options display either poor efficacy or life‐threatening side effects. There is clear evidence that relapsing‐remitting clinic...

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Bibliographic Details
Published in:ChemMedChem 2020-11, Vol.15 (21), p.1985-2003
Main Authors: Maramai, Samuele, Brindisi, Margherita
Format: Article
Language:English
Subjects:
Animal models
Central nervous system
Demyelination
endocannabinoid
Endocannabinoid system
fatty acid amide hydrolas
Immunomodulation
Immunotherapy
Inflammation
Metabolism
Modulators
monoacylglycerol lipas
Multiple sclerosis
Neurodegeneration
Neuromodulation
Oxidative stress
Side effects
State-of-the-art reviews
Target recognition
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Summary:Multiple sclerosis (MS) is a chronic, immune‐mediated disease of the central nervous system. At present, there is no definitive cure, and the few available disease‐modifying options display either poor efficacy or life‐threatening side effects. There is clear evidence that relapsing‐remitting clinical attacks in MS are driven by inflammatory demyelination and that the subsequent disease steps, being irresponsive to immunotherapy, result from neurodegeneration. The endocannabinoid system (ECS) stands halfway between three key pathomechanisms underlying MS, namely inflammation, neurodegeneration and oxidative stress, thus representing a kingpin for the identification of novel therapeutic targets in MS. This review summarizes the current state of the art in the field of endocannabinoid metabolism modulators and their in vivo effects on relevant animal models. We also highlight key molecular underpinnings of their therapeutic efficacy as well as the potential to turn them into promising clinical candidates. Endocannabinoids and MS: This review offers a special focus on the modulation of the endogenous levels of endocannabinoids as a novel treatment option for multiple sclerosis. An overview on endocannabinoid metabolism modulators and their in vivo effects on relevant animal models is provided. This paper also highlights key molecular underpinnings of their therapeutic efficacy and critically discusses the potential to turn them into robust clinical candidates.
ISSN:1860-7179
1860-7187
DOI:10.1002/cmdc.202000310