Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 18, Issue 10, Pages -Publisher
MDPI
DOI: 10.3390/ijms18102128
Keywords
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
Funding
- Italian Ministry of University and Research [2015TM24JS_009]
- SYSBIONET-Italian ROADMAP ESFRI Infrastructures
- Blueprint Pharma Societa a Responsabilita Limitata
- PRIMM
- Regione Campania
- Consiglio Nazionale delle Ricerche
- Italian Ministry of University and Research [2015TM24JS_009]
- SYSBIONET-Italian ROADMAP ESFRI Infrastructures
- Blueprint Pharma Societa a Responsabilita Limitata
- PRIMM
- Regione Campania
- Consiglio Nazionale delle Ricerche
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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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