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Thrombin generation and activity in multiple sclerosis.
Jordan, Kelley R; Parra-Izquierdo, Ivan; Gruber, András; Shatzel, Joseph J; Pham, Peter; Sherman, Larry S; McCarty, Owen J T; Verbout, Norah G.
Afiliação
  • Jordan KR; Department of Biomedical Engineering, Oregon Health and Science University, School of Medicine, 3303 SW Bond Avenue, Portland, OR, 97239, USA. Jordake@ohsu.edu.
  • Parra-Izquierdo I; Department of Biomedical Engineering, Oregon Health and Science University, School of Medicine, 3303 SW Bond Avenue, Portland, OR, 97239, USA.
  • Gruber A; Division of Hematology and Medical Oncology, Oregon Health and Science University, Knight Cancer Institute, Portland, OR, USA.
  • Shatzel JJ; Department of Biomedical Engineering, Oregon Health and Science University, School of Medicine, 3303 SW Bond Avenue, Portland, OR, 97239, USA.
  • Pham P; Division of Hematology and Medical Oncology, Oregon Health and Science University, Knight Cancer Institute, Portland, OR, USA.
  • Sherman LS; Aronora Inc, Portland, OR, USA.
  • McCarty OJT; Department of Biomedical Engineering, Oregon Health and Science University, School of Medicine, 3303 SW Bond Avenue, Portland, OR, 97239, USA.
  • Verbout NG; Division of Hematology and Medical Oncology, Oregon Health and Science University, Knight Cancer Institute, Portland, OR, USA.
Metab Brain Dis ; 36(3): 407-420, 2021 03.
Article em En | MEDLINE | ID: mdl-33411219
The coagulation cascade and immune system are intricately linked, highly regulated and respond cooperatively in response to injury and infection. Increasingly, evidence of hyper-coagulation has been associated with autoimmune disorders, including multiple sclerosis (MS). The pathophysiology of MS includes immune cell activation and recruitment to the central nervous system (CNS) where they degrade myelin sheaths, leaving neuronal axons exposed to damaging inflammatory mediators. Breakdown of the blood-brain barrier (BBB) facilitates the entry of peripheral immune cells. Evidence of thrombin activity has been identified within the CNS of MS patients and studies using animal models of experimental autoimmune encephalomyelitis (EAE), suggest increased thrombin generation and activity may play a role in the pathogenesis of MS as well as inhibit remyelination processes. Thrombin is a serine protease capable of cleaving multiple substrates, including protease activated receptors (PARs), fibrinogen, and protein C. Cleavage of all three of these substrates represent pathways through which thrombin activity may exert immuno-regulatory effects and regulate permeability of the BBB during MS and EAE. In this review, we summarize evidence that thrombin activity directly, through PARs, and indirectly, through fibrin formation and activation of protein C influences neuro-immune responses associated with MS and EAE pathology.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Barreira Hematoencefálica / Trombina / Encefalomielite Autoimune Experimental / Esclerose Múltipla Limite: Animals / Humans Idioma: En Revista: Metab Brain Dis Assunto da revista: CEREBRO / METABOLISMO Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Barreira Hematoencefálica / Trombina / Encefalomielite Autoimune Experimental / Esclerose Múltipla Limite: Animals / Humans Idioma: En Revista: Metab Brain Dis Assunto da revista: CEREBRO / METABOLISMO Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Estados Unidos