Neuro-Coagulopathy: Blood Coagulation Factors in Central Nervous System Diseases

被引:70
|
作者
De Luca, Ciro [1 ]
Virtuoso, Assunta [1 ]
Maggio, Nicola [2 ,3 ,4 ]
Papa, Michele [1 ,5 ]
机构
[1] Univ Campania Luigi Vanvitelli, Lab Neuronal Networks, I-80138 Naples, Italy
[2] Chaim Sheba Med Ctr, Dept Neurol, IL-52621 Tel Hashomer, Israel
[3] Tel Aviv Univ, Sackler Fac Med, Dept Neurol & Neurosurg, IL-6997801 Tel Aviv, Israel
[4] Tel Aviv Univ, Sagol Sch Neurosci, IL-6997801 Tel Aviv, Israel
[5] Univ Milano Bicocca, Ctr Syst Biol, SYSBIO, I-20126 Milan, Italy
关键词
coagulation; thrombin; proteinase activated receptors; activated protein C; amyotrophic lateral sclerosis; Alzheimer's disease; Parkinson's disease; multiple sclerosis; ischemic stroke; post-ischemic epilepsy; CNS cancer; addiction; mental health; PROTEASE-ACTIVATED RECEPTOR-1; AMYOTROPHIC-LATERAL-SCLEROSIS; TISSUE-PLASMINOGEN ACTIVATOR; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; CORONARY-ARTERY-DISEASE; TRAUMATIC BRAIN-INJURY; LONG-TERM-POTENTIATION; MULTIPLE-SCLEROSIS; ALZHEIMERS-DISEASE; SYNAPTIC PLASTICITY;
D O I
10.3390/ijms18102128
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Blood coagulation factors and other proteins, with modulatory effects or modulated by the coagulation cascade have been reported to affect the pathophysiology of the central nervous system (CNS). The protease-activated receptors (PARs) pathway can be considered the central hub of this regulatory network, mainly through thrombin or activated protein C (aPC). These proteins, in fact, showed peculiar properties, being able to interfere with synaptic homeostasis other than coagulation itself. These specific functions modulate neuronal networks, acting both on resident (neurons, astrocytes, and microglia) as well as circulating immune system cells and the extracellular matrix. The pleiotropy of these effects is produced through different receptors, expressed in various cell types, in a dose- and time-dependent pattern. We reviewed how these pathways may be involved in neurodegenerative diseases (amyotrophic lateral sclerosis, Alzheimer's and Parkinson's diseases), multiple sclerosis, ischemic stroke and post-ischemic epilepsy, CNS cancer, addiction, and mental health. These data open up a new path for the potential therapeutic use of the agonist/antagonist of these proteins in the management of several central nervous system diseases.
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页数:24
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