Title :

Safe and Efficient Sigma1 Ligand: A Potential Drug Candidate for Multiple Sclerosis.

Author(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 - U 1011 [RNMCD]
Odou, Pascal [Auteur]
Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 [GRITA]
Duhal, Nathalie [Auteur]
Université Lille Nord (France)
Ninni, Sandro [Auteur]
Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U 1011 [RNMCD]
Montaigne, David [Auteur]
Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 [RNMCD]
Delhem, Nadira [Auteur]
Thérapies Assistées par Lasers et Immunothérapies pour l'Oncologie - U 1189 [OncoThAI]
Vermersch, Patrick [Auteur]
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 [JPArc]
Melnyk, Patricia [Auteur]
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 [JPArc]

Journal title :

International Journal of Molecular Sciences

Pages :

11893

Publisher :

MDPI

Publication date :

2022-10-16

ISSN :

1661-6596

Keyword(s) :

benzamide
sigma1 receptor
CNS
multiple sclerosis

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [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 ...
Show more >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.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

ANR Project :

SATT NORD

Collections :

• Thérapies Lasers Assistées par l'Image pour l'Oncologie (ONCO-THAI) - U1189

Source :

Harvested from HAL