BTK inhibition limits microglia-perpetuated CNS inflammation and promotes myelin repair.
Acta Neuropathol
; 147(1): 75, 2024 04 24.
Article
en En
| MEDLINE
| ID: mdl-38656399
ABSTRACT
In multiple sclerosis (MS), persisting disability can occur independent of relapse activity or development of new central nervous system (CNS) inflammatory lesions, termed chronic progression. This process occurs early and it is mostly driven by cells within the CNS. One promising strategy to control progression of MS is the inhibition of the enzyme Bruton's tyrosine kinase (BTK), which is centrally involved in the activation of both B cells and myeloid cells, such as macrophages and microglia. The benefit of BTK inhibition by evobrutinib was shown as we observed reduced pro-inflammatory activation of microglia when treating chronic experimental autoimmune encephalomyelitis (EAE) or following the adoptive transfer of activated T cells. Additionally, in a model of toxic demyelination, evobrutinib-mediated BTK inhibition promoted the clearance of myelin debris by microglia, leading to an accelerated remyelination. These findings highlight that BTK inhibition has the potential to counteract underlying chronic progression of MS.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Piperidinas
/
Pirimidinas
/
Microglía
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Encefalomielitis Autoinmune Experimental
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Agammaglobulinemia Tirosina Quinasa
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Vaina de Mielina
Límite:
Animals
Idioma:
En
Revista:
Acta Neuropathol
Año:
2024
Tipo del documento:
Article
País de afiliación:
Alemania