Safe and Efficient Sigma1 Ligand: A Potential ...
Type de document :
Article dans une revue scientifique: Article original
DOI :
PMID :
URL permanente :
Titre :
Safe and Efficient Sigma1 Ligand: A Potential Drug Candidate for Multiple Sclerosis.
Auteur(s) :
Oxombre, Bénédicte [Auteur]
Lille Neurosciences & Cognition - U 1172 [LilNCog]
Madouri, Farima [Auteur]
Lille Neurosciences & Cognition - U 1172 [LilNCog]
Journe, Anne-Sophie [Auteur]
Lille Neurosciences & Cognition - U 1172 [LilNCog]
Ravez, Severine [Auteur]
Lille Neurosciences & Cognition - U 1172 [LilNCog]
Woitrain, Eloise [Auteur]
Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U1011 [RNMCD]
Odou, Pascal [Auteur]
Groupe de Recherche sur les formes Injectables et les Technologies Associées (GRITA) - ULR 7365
Duhal, Nathalie [Auteur]
Université Lille Nord (France)
Ninni, Sandro [Auteur]
Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U1011 [RNMCD]
Montaigne, David [Auteur]
Récepteurs nucléaires, Maladies Cardiovasculaires et Diabète (EGID) - U1011
Delhem, Nadira [Auteur]
Thérapies Laser Assistées par l'Image pour l'Oncologie - U 1189 [ONCO-THAI]
Vermersch, Patrick [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Melnyk, Patricia [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Lille Neurosciences & Cognition - U 1172 [LilNCog]
Madouri, Farima [Auteur]
Lille Neurosciences & Cognition - U 1172 [LilNCog]
Journe, Anne-Sophie [Auteur]
Lille Neurosciences & Cognition - U 1172 [LilNCog]
Ravez, Severine [Auteur]
Lille Neurosciences & Cognition - U 1172 [LilNCog]
Woitrain, Eloise [Auteur]
Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U1011 [RNMCD]
Odou, Pascal [Auteur]
Groupe de Recherche sur les formes Injectables et les Technologies Associées (GRITA) - ULR 7365
Duhal, Nathalie [Auteur]
Université Lille Nord (France)
Ninni, Sandro [Auteur]
Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U1011 [RNMCD]
Montaigne, David [Auteur]
Récepteurs nucléaires, Maladies Cardiovasculaires et Diabète (EGID) - U1011
Delhem, Nadira [Auteur]
Thérapies Laser Assistées par l'Image pour l'Oncologie - U 1189 [ONCO-THAI]
Vermersch, Patrick [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Melnyk, Patricia [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Titre de la revue :
International Journal of Molecular Sciences
Nom court de la revue :
Int J Mol Sci
Numéro :
23
Pagination :
11893
Éditeur :
MDPI
Date de publication :
2022-10-16
ISSN :
1422-0067
Mot(s)-clé(s) :
benzamide
sigma1 receptor
CNS
multiple sclerosis
sigma1 receptor
CNS
multiple sclerosis
Discipline(s) HAL :
Sciences du Vivant [q-bio]
Résumé en anglais : [en]
Multiple Sclerosis (MS) is an autoimmune demyelinating and neurodegenerative disease of the central nervous system (CNS). Current management strategies suppress or modulate immune function, all with consequences and known ...
Lire la suite >Multiple Sclerosis (MS) is an autoimmune demyelinating and neurodegenerative disease of the central nervous system (CNS). Current management strategies suppress or modulate immune function, all with consequences and known side effects. They demonstrate a high level of success in limiting new relapses. However, the neurodegenerative process still affects both grey and white matter in the central nervous system. The sigma1 (S1R) ligand-regulated chaperone is implicated in many biological processes in various CNS-targeted diseases, acting on neural plasticity, myelination and neuroinflammation. Among the proteins involved in MS, S1R has therefore emerged as a promising new target. Standard and robust methods have been adopted to analyze the adsorption, distribution, metabolism, excretion (ADME) properties, safety pharmacology and toxicology of a previously synthetized simple benzamide-derived compound with nanomolar affinity for S1R, high selectivity, no cytotoxicity and good metabolic stability. The compound was also characterized as an agonist based on well-validated assays prior to in vivo investigations. Interestingly, we found that the oral administration of this compound resulted in an overall significant reduction in clinical progression in an MS experimental model. This effect is mediated through S1R action. Our results further suggest the potential use of this compound in the treatment of MS.Lire moins >
Lire la suite >Multiple Sclerosis (MS) is an autoimmune demyelinating and neurodegenerative disease of the central nervous system (CNS). Current management strategies suppress or modulate immune function, all with consequences and known side effects. They demonstrate a high level of success in limiting new relapses. However, the neurodegenerative process still affects both grey and white matter in the central nervous system. The sigma1 (S1R) ligand-regulated chaperone is implicated in many biological processes in various CNS-targeted diseases, acting on neural plasticity, myelination and neuroinflammation. Among the proteins involved in MS, S1R has therefore emerged as a promising new target. Standard and robust methods have been adopted to analyze the adsorption, distribution, metabolism, excretion (ADME) properties, safety pharmacology and toxicology of a previously synthetized simple benzamide-derived compound with nanomolar affinity for S1R, high selectivity, no cytotoxicity and good metabolic stability. The compound was also characterized as an agonist based on well-validated assays prior to in vivo investigations. Interestingly, we found that the oral administration of this compound resulted in an overall significant reduction in clinical progression in an MS experimental model. This effect is mediated through S1R action. Our results further suggest the potential use of this compound in the treatment of MS.Lire moins >
Langue :
Anglais
Audience :
Internationale
Établissement(s) :
Université de Lille
CHU Lille
CHU Lille
Collections :
Date de dépôt :
2023-05-25T02:25:18Z
2023-06-28T12:24:04Z
2023-06-28T12:24:04Z
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