Inhibition of N-acylethanolamine-hydrolyzing acid amidase reduces T cell infiltration in a mouse model of multiple sclerosis.
Pharmacol Res
; 172: 105816, 2021 10.
Article
en En
| MEDLINE
| ID: mdl-34391933
ABSTRACT
Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis (MS), in which myeloid cells sustain inflammation, take part in priming, differentiation, and reactivation of myelin-specific T cells, and cause direct myelin damage. N-Acylethanolamine-hydrolyzing acid amidase (NAAA) is a proinflammatory enzyme induced by phlogosis and overexpressed in macrophages and microglia of EAE mice. Targeting these cell populations by inhibiting NAAA may be a promising pharmacological strategy to modulate the inflammatory aspect of MS and manage disease progression. To address this goal, we used ARN16186, a small molecule specifically designed and synthesized as a pharmacological tool to inhibit NAAA. We assessed whether enzyme inhibition affected the severity of neurological symptoms and modulated immune cell infiltration into the central nervous system of EAE mice. We found that preventive chronic treatment with ARN16186 was efficacious in slowing disease progression and preserving locomotor activity in EAE mice. Furthermore, NAAA inhibition reduced the number of immune cells infiltrating the spinal cord and modulated the overactivation of NF-kB and STAT3 transcription factors, leading to less expansion of Th17 cells over the course of the disease.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Linfocitos T
/
Encefalomielitis Autoinmune Experimental
/
Amidohidrolasas
/
Esclerosis Múltiple
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Pharmacol Res
Asunto de la revista:
FARMACOLOGIA
Año:
2021
Tipo del documento:
Article
País de afiliación:
Italia