Hemostasis Components as Therapeutic Targets in Autoimmune Demyelination

Abbadessa, Gianmarco; Mainero, Caterina; Bonavita, Simona

doi:10.1002/cpt.2532

Cited by 4 publications

(1 citation statement)

References 84 publications

(234 reference statements)

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“…Additionally, fibrin upregulates ICAM-1 expression on the endothelial cell surface, facilitating arrest and recruitment of immune cells to sites of compromised barrier function [8,58]. Although imaging fibrinogen deposition in the neurovasculature holds promise for the study of the neuroimmune mechanisms driving neurodegeneration in disease [59,60], targeting fibrinogen or the mechanisms of fibrin formation as a therapy for multiple sclerosis has been hampered by selectivity, specificity, and drug-delivery challenges [61 ▪ ].…”

Section: Role Of Coagulation Factors In Blood–brain Barrier Functionmentioning

confidence: 99%

Factor XI as a therapeutic target in neuroinflammatory disease

Taskin,

Kohs,

Shatzel

et al. 2023

Current Opinion in Hematology

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Purpose of review This review summarizes the pathophysiology and potential therapeutic options for treatment of multiple sclerosis, a common neuronal demyelinating disorder affecting 2.2 million people worldwide. As an autoimmune disorder, multiple sclerosis is associated with neuroinflammation and increased permeability of the blood–brain barrier (BBB), although the cause linking multiple sclerosis with compromised barrier function remains ill-defined. It has been previously shown that coagulation factors, including thrombin and fibrin, exacerbate the inflammatory processes and permeability of the BBB. Recent findings Increased levels of the coagulation factor (F) XII have been found in patients presenting with relapsing–remitting multiple sclerosis, with a deleterious role for FXII being validated in murine model of multiple sclerosis, experimental autoimmune encephalitis (EAE). Recent work has uncovered a role for the major substrate activated by FXII and thrombin, FXI, in the disorder of EAE. The study found that pharmacological targeting of FXI decreased clinical symptoms, lymphocyte invasion, and white matter destruction in a multiple sclerosis model. Summary This review emphasizes the role of FXII and FXI in regulating barrier function and the immune response in neuroinflammation. These new findings broaden the potential for therapeutic utility of FXI inhibitors beyond thrombosis to include neuroinflammatory diseases associated with compromised BBB function, including multiple sclerosis.

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Section: Role Of Coagulation Factors In Blood–brain Barrier Functionmentioning

confidence: 99%

Factor XI as a therapeutic target in neuroinflammatory disease

Taskin,

Kohs,

Shatzel

et al. 2023

Current Opinion in Hematology

View full text Add to dashboard Cite

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In vivo and in silico studies of membrane-stabilizing and clot lysis activities of Trachyspermum ammi

Akbor,

Haque,

Rahman

et al. 2024

Food Chemistry Advances

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Gut Microbiome and Circadian Interactions with Platelets Across Human Diseases, including Alzheimer’s Disease, Amyotrophic Lateral Sclerosis, and Cancer

Anderson

2023

CTMC

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Platelets have traditionally been investigated for their role in clot formation in the course of cardiovascular diseases and strokes. However, recent work indicates platelets to be an integral aspect of wider systemic processes, with relevance to the pathophysiology of a host of diverse medical conditions, including neurodegenerative disorders and cancer. This article reviews platelet function and interactions with the gut microbiome and circadian systems, highlighting the role of the platelet mitochondrial melatonergic pathway in determining platelet activation, fluxes and plasticity. This provides a number of novel conceptualizations of platelet function and mode of interaction with other cell types, including the pathoetiology and pathophysiology of diverse medical conditions, such as cancer, Alzheimer’s disease, and amyotrophic lateral sclerosis. It is proposed that a platelet-gut axis allows platelets to contribute to many of the pathophysiological processes linked to gut dysbiosis and gut permeability. This is at least partly via platelet sphingosine- 1-phosphate release, which regulates enteric glial cells and lymphocyte chemotaxis, indicating an etiological role for platelets in a wide array of medical conditions linked to alterations in the gut microbiome. Platelets are also an important regulator of the various microenvironments that underpin most human medical conditions, including the tumor microenvironment, neurodegenerative diseases, and autoimmune disorders. Platelet serotonin release regulates the availability of the mitochondrial melatonergic pathway systemically, thereby being an important determinant of the dynamic metabolic interactions occurring across cell types that underpin the pathoetiology of many medical conditions. In addition, a number of novel and diverse future research directions and treatment implications are proposed.

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Hemostasis Components as Therapeutic Targets in Autoimmune Demyelination

Cited by 4 publications

References 84 publications

Factor XI as a therapeutic target in neuroinflammatory disease

Factor XI as a therapeutic target in neuroinflammatory disease

In vivo and in silico studies of membrane-stabilizing and clot lysis activities of Trachyspermum ammi

Gut Microbiome and Circadian Interactions with Platelets Across Human Diseases, including Alzheimer’s Disease, Amyotrophic Lateral Sclerosis, and Cancer

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