The Evolving Concept of Neuro-Thromboinflammation for Neurodegenerative Disorders and Neurotrauma: A Rationale for PAR1-Targeting Therapies
Abstract
:1. Introduction to Neuro-Thromboinflammation and Historical Background
1.1. The Interaction between Inflammation and Coagulation Is a Continuum
1.2. The Coevolution of Coagulation, Innate Immunity, and Inflammation
1.3. Clinical Identification and Application of the Coag-Inflamm Nexus
2. Key Players in Neuro-Thromboinflammation
2.1. Tissue Factor (TF)
2.2. Pathogen-Associated Molecular Patterns (PAMPs)
2.3. DAMPS, Key in Acute and Chronic Neuro-Thromboinflammation
2.4. Thrombomodulin (TM), Activated Protein C (APC), and Endothelial Cell PC Receptor (EPCR)
2.5. Intact and Damaged Microvascular Endothelium
2.6. Protease-Activated Receptors (PARs)
2.7. Biased PAR1 Signaling
3. PAR1, APC, and Neurodegeneration
BBB Dysfunction in Neurodegenerative Diseases and APC as a Therapeutic
4. Other PAR1 Ligands with Potential Neuroprotective Activity
4.1. Orthosteric PAR1 Antagonists and Inhibitors of PAR1/Thrombin Binding
4.2. Anti-Inflammatory PAR1 N-Terminal Peptides
4.3. Pepducins
4.4. Parmodulins
5. Additional Rationale for PAR1 as a Therapeutic Target for ALS
6. Concluding Remarks
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Festoff, B.W.; Dockendorff, C. The Evolving Concept of Neuro-Thromboinflammation for Neurodegenerative Disorders and Neurotrauma: A Rationale for PAR1-Targeting Therapies. Biomolecules 2021, 11, 1558. https://doi.org/10.3390/biom11111558
Festoff BW, Dockendorff C. The Evolving Concept of Neuro-Thromboinflammation for Neurodegenerative Disorders and Neurotrauma: A Rationale for PAR1-Targeting Therapies. Biomolecules. 2021; 11(11):1558. https://doi.org/10.3390/biom11111558
Chicago/Turabian StyleFestoff, Barry W., and Chris Dockendorff. 2021. "The Evolving Concept of Neuro-Thromboinflammation for Neurodegenerative Disorders and Neurotrauma: A Rationale for PAR1-Targeting Therapies" Biomolecules 11, no. 11: 1558. https://doi.org/10.3390/biom11111558