Thrombin and the Coag-Inflammatory Nexus in Neurotrauma, ALS, and Other Neurodegenerative Disorders

Frontiers in Neurology
Barry W Festoff, Bruce A Citron

Abstract

This review details our current understanding of thrombin signaling in neurodegeneration, with a focus on amyotrophic lateral sclerosis (ALS, Lou Gehrig's disease) as well as future directions to be pursued. The key factors are multifunctional and involved in regulatory pathways, namely innate immune and the coagulation cascade activation, that are essential for normal nervous system function and health. These two major host defense systems have a long history in evolution and include elements and regulators of the coagulation pathway that have significant impacts on both the peripheral and central nervous system in health and disease. The clotting cascade responds to a variety of insults to the CNS including injury and infection. The blood brain barrier is affected by these responses and its compromise also contributes to these detrimental effects. Important molecules in signaling that contribute to or protect against neurodegeneration include thrombin, thrombomodulin (TM), protease activated receptor 1 (PAR1), damage associated molecular patterns (DAMPs), such as high mobility group box protein 1 (HMGB1) and those released from mitochondria (mtDAMPs). Each of these molecules are entangled in choices dependent upon specific si...Continue Reading

References

Sep 1, 1979·Journal of Neurobiology·H L FernandezB W Festoff
Feb 1, 1979·Journal of Neurochemistry·H L FernandezB W Festoff
Sep 1, 1992·Toxicon : Official Journal of the International Society on Toxinology·C OuyangT F Huang
Oct 1, 1992·Neuropathology and Applied Neurobiology·V H Perry, P B Andersson
Dec 1, 1992·Journal of the Neurological Sciences·L T KurlandP N Nemetz
Jan 1, 1992·Mammalian Genome : Official Journal of the International Mammalian Genome Society·H WichmannK Kaupmann
Aug 9, 1991·Brain Research·V L WongM Fisher
Apr 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·D HantaïB W Festoff
Jan 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·D HantaïB W Festoff
May 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·D Gurwitz, D D Cunningham
Aug 1, 1985·The New England Journal of Medicine·P M HoffmanF W Ruscetti
Jan 1, 1986·Annals of the New York Academy of Sciences·E D Means, D K Anderson
Jan 1, 1973·The British Journal of Psychiatry : the Journal of Mental Science·I I Gottesman, J Shields
Jan 1, 1980·Journal of Neurobiology·H L FernandezB W Festoff
Jan 1, 1981·Muscle & Nerve·B W Festoff, H L Fernandez
Dec 20, 1994·Journal of the Neurological Sciences·I V Smirnova, B W Festoff
Jul 1, 1994·Journal of the Neurological Sciences·S H AppelE Stefani
Jan 31, 1995·Proceedings of the National Academy of Sciences of the United States of America·L J HouenouB W Festoff
Jan 1, 1994·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·G J HoB W Festoff
Jan 1, 1994·Seminars in Thrombosis and Hemostasis·I V SmirnovaB W Festoff
Jan 1, 1994·Annual Review of Immunology·P Matzinger
Apr 1, 1994·Journal of Cellular Physiology·B W FestoffJ Chao
Apr 12, 1994·Proceedings of the National Academy of Sciences of the United States of America·R G SmithS H Appel
Mar 1, 1994·Journal of Neurobiology·Y LiuP G Nelson

❮ Previous
Next ❯

Citations

Jul 16, 2020·Cells·Bernardo L RapoportRonald Anderson
Apr 5, 2020·International Journal of Molecular Sciences·Valery GoldermanEfrat Shavit-Stein
Aug 10, 2019·Neural Regeneration Research·Shany G Gofrit, Efrat Shavit-Stein
Jul 1, 2020·Neural Regeneration Research·George Zaki Ghali, Michael George Zaki Ghali
Dec 4, 2020·Neural Regeneration Research·Elena Pompili, Cinzia Fabrizi
Jan 5, 2021·Cellular and Molecular Neurobiology·Hui CaoWenting Song
Jul 31, 2020·Current Drug Targets·Shu WangTianfu Li

❮ Previous
Next ❯

Methods Mentioned

BETA
gene-knockout
glycosylation
transgenics
transgenic
GTPase
PCR
genotyping

Software Mentioned

PHLOGISTIX

Related Concepts

Related Feeds

Blood Coagulation Signaling Pathways

Coagulation is the process by which a blood clot is formed. This process includes both the formation of a platelet plug as well as a cascade of clotting factors resulting in the formation of fibrin strands. Find the latest research on coagulation signaling pathways here.

Blood Clotting Disorders

Thrombophilia includes conditions with increased tendency for excessive blood clotting. Blood clotting occurs when the body has insufficient amounts of specialized proteins that make blood clot and stop bleeding. Here is the latest research on blood clotting disorders.

ALS: Pathogenic Mechanisms

Amyotrophic Lateral Sclerosis is a progressive neurodegenerative disorder characterized by muscle weakness. Here is the latest research investigating pathogenic mechanisms that underlie this genetically heterogeneous disorder.

Brain Injury & Trauma

brain injury after impact to the head is due to both immediate mechanical effects and delayed responses of neural tissues.

Amyloid Lateral Sclerosis

Amyotrophic Lateral Sclerosis (ALS) is a progressive nervous system disease associated with the death of neurons that control voluntary muscles. Discover the latest research on ALS here.