ABHD6-aren inhibizioaren azterketa birmielinizazioa bultzatzeko kuprizonaren desmielinizazio primarioaren aniamalia-ereduan.

Resumen

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the nervouse central system (CNS). Although the ethiology of the disease remains unknown, of the main hallmarks is the appearance of inflammatory lesions related to the death of oligodendrocytes and neurodegeneration. Those events are, indeed, the cause of disability in the patients. However, there is a partial recovery of the myelin, and nowadays the efforts are focused on finding strategies to enhance this repair. During the last years, numerous researches have shown the potential of the endocannabinoid system to reduce the symptomatology of MS. In this sense, the inhibition of the degradation of 2-arachidonoylglycerol (2-AG) seems the most promising strategy. Monoacylglycerol lipase (MAGL) degrades the majority of the 2-AG in the CNS. Although the blockade of this enzyme protects against demyelination and promotes remyelination, it also induces desensitization of CB1 receptors. Even though in basal conditions alpha/beta-Hydrolase containing domain 6 (ABHD6) hydrolyses a small quantity of 2-AG, it degrades a bigger amount under inflammatory conditions. Thus, ABHD6 inhibition is proposed in inflammatory contexts in order to increase 2-AG levels while avoiding side effects. With this aim, we study the remyelination potential of KT182, a specific ABHD6 inhibitor, in an animal model of MS.