Could Mycolactone Inspire New Potent ...
Document type :
Compte-rendu et recension critique d'ouvrage
DOI :
PMID :
Title :
Could Mycolactone Inspire New Potent Analgesics? Perspectives and Pitfalls
Author(s) :
Reynaert, Marie-Line [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Dupoiron, Denis [Auteur]
Institut de Cancérologie de l'Ouest [Angers/Nantes] [UNICANCER/ICO]
Yeramian, Edouard [Auteur]
Microbiologie structurale - Structural Microbiology [Microb. Struc. (UMR_3528 / U-Pasteur_5)]
Marsollier, Laurent [Auteur correspondant]
ATOMycA [CRCINA-ÉQUIPE 6]
Brodin, Priscille [Auteur correspondant]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Dupoiron, Denis [Auteur]
Institut de Cancérologie de l'Ouest [Angers/Nantes] [UNICANCER/ICO]
Yeramian, Edouard [Auteur]
Microbiologie structurale - Structural Microbiology [Microb. Struc. (UMR_3528 / U-Pasteur_5)]
Marsollier, Laurent [Auteur correspondant]
ATOMycA [CRCINA-ÉQUIPE 6]
Brodin, Priscille [Auteur correspondant]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Journal title :
TOXINS
Pages :
516
Publisher :
MDPI
Publication date :
2019-09-04
English keyword(s) :
AT2R
drug development
neurons
analgesia
mycolactone
drug development
neurons
analgesia
mycolactone
HAL domain(s) :
Sciences du Vivant [q-bio]/Cancer
English abstract : [en]
Pain currently represents the most common symptom for which medical attention is sought by patients. The available treatments have limited effectiveness and significant side-effects. In addition, most often, the duration ...
Show more >Pain currently represents the most common symptom for which medical attention is sought by patients. The available treatments have limited effectiveness and significant side-effects. In addition, most often, the duration of analgesia is short. Today, the handling of pain remains a major challenge. One promising alternative for the discovery of novel potent analgesics is to take inspiration from Mother Nature; in this context, the detailed investigation of the intriguing analgesia implemented in Buruli ulcer, an infectious disease caused by the bacterium Mycobacterium ulcerans and characterized by painless ulcerative lesions, seems particularly promising. More precisely, in this disease, the painless skin ulcers are caused by mycolactone, a polyketide lactone exotoxin. In fact, mycolactone exerts a wide range of effects on the host, besides being responsible for analgesia, as it has been shown notably to modulate the immune response or to provoke apoptosis. Several cellular mechanisms and different targets have been proposed to account for the analgesic effect of the toxin, such as nerve degeneration, the inhibition of inflammatory mediators and the activation of angiotensin II receptor 2. In this review, we discuss the current knowledge in the field, highlighting possible controversies. We first discuss the different pain-mimicking experimental models that were used to study the effect of mycolactone. We then detail the different variants of mycolactone that were used in such models. Overall, based on the results and the discussions, we conclude that the development of mycolactone-derived molecules can represent very promising perspectives for new analgesic drugs, which could be effective for specific pain indications. Key Contribution: This review develops arguments and issues around the development of new potent analgesic drugs derived from mycolactone, a toxin secreted by Mycobacterium ulcerans. To this end, the various modes of action of the toxin potentially underlying its analgesic properties are detailed and discussed in the context of various pain models-also concerning different variants of mycolactone.Show less >
Show more >Pain currently represents the most common symptom for which medical attention is sought by patients. The available treatments have limited effectiveness and significant side-effects. In addition, most often, the duration of analgesia is short. Today, the handling of pain remains a major challenge. One promising alternative for the discovery of novel potent analgesics is to take inspiration from Mother Nature; in this context, the detailed investigation of the intriguing analgesia implemented in Buruli ulcer, an infectious disease caused by the bacterium Mycobacterium ulcerans and characterized by painless ulcerative lesions, seems particularly promising. More precisely, in this disease, the painless skin ulcers are caused by mycolactone, a polyketide lactone exotoxin. In fact, mycolactone exerts a wide range of effects on the host, besides being responsible for analgesia, as it has been shown notably to modulate the immune response or to provoke apoptosis. Several cellular mechanisms and different targets have been proposed to account for the analgesic effect of the toxin, such as nerve degeneration, the inhibition of inflammatory mediators and the activation of angiotensin II receptor 2. In this review, we discuss the current knowledge in the field, highlighting possible controversies. We first discuss the different pain-mimicking experimental models that were used to study the effect of mycolactone. We then detail the different variants of mycolactone that were used in such models. Overall, based on the results and the discussions, we conclude that the development of mycolactone-derived molecules can represent very promising perspectives for new analgesic drugs, which could be effective for specific pain indications. Key Contribution: This review develops arguments and issues around the development of new potent analgesic drugs derived from mycolactone, a toxin secreted by Mycobacterium ulcerans. To this end, the various modes of action of the toxin potentially underlying its analgesic properties are detailed and discussed in the context of various pain models-also concerning different variants of mycolactone.Show less >
Language :
Anglais
Popular science :
Non
Source :
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