C-reactive protein: the nexus between inflammation and protein misfolding diseases
C-reactive protein (CRP), an acute-phase protein primarily produced by hepatocytes in response to pro-inflammatory cytokines, is a widely used clinical marker for inflammation and tissue damage. In its native state, CRP exists in a stable pentameric form called pCRP. Upon interaction with activated...
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Frontiers Media S.A.
2025-06-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1612703/full |
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| author | Abhishek Roy Abhishek Roy Johannes Zeller Johannes Zeller Tracy L. Nero Tracy L. Nero Tracy L. Nero Johanna Klepetko Steffen U. Eisenhardt Michael W. Parker Michael W. Parker Michael W. Parker James D. McFadyen James D. McFadyen James D. McFadyen James D. McFadyen Karlheinz Peter Karlheinz Peter Karlheinz Peter Karlheinz Peter |
| author_facet | Abhishek Roy Abhishek Roy Johannes Zeller Johannes Zeller Tracy L. Nero Tracy L. Nero Tracy L. Nero Johanna Klepetko Steffen U. Eisenhardt Michael W. Parker Michael W. Parker Michael W. Parker James D. McFadyen James D. McFadyen James D. McFadyen James D. McFadyen Karlheinz Peter Karlheinz Peter Karlheinz Peter Karlheinz Peter |
| author_sort | Abhishek Roy |
| collection | DOAJ |
| description | C-reactive protein (CRP), an acute-phase protein primarily produced by hepatocytes in response to pro-inflammatory cytokines, is a widely used clinical marker for inflammation and tissue damage. In its native state, CRP exists in a stable pentameric form called pCRP. Upon interaction with activated cell membranes, pCRP undergoes a transitional conformation change into activated pCRP (pCRP*) and subsequently fully dissociates into its monomeric subunits (mCRP). pCRP* and mCRP interact with C1q and thereby activate the classical complement system pathway and both exert pro-inflammatory effects on platelets and endothelial cells. Although classically recognized as a marker of acute inflammation, CRP is increasingly implicated in the pathogenesis of protein-misfolding pathologies, notably neurodegenerative diseases and amyloidosis. This review explores the complex interplay between CRP, encompassing its isoforms pCRP, pCRP*, and mCRP, and misfolded proteins, examining the specific contributions to inflammation and neurodegenerative disease pathogenesis. We analyze the clinical significance of variations in CRP levels in patients with protein-misfolding diseases, discuss underlying mechanisms, and highlight potential implications of these findings for drug discovery and therapeutic targeting of CRP. |
| format | Article |
| id | doaj-art-db88f46c38d54c158bd10bce312fbc67 |
| institution | OA Journals |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-db88f46c38d54c158bd10bce312fbc672025-08-20T02:32:04ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-06-011610.3389/fimmu.2025.16127031612703C-reactive protein: the nexus between inflammation and protein misfolding diseasesAbhishek Roy0Abhishek Roy1Johannes Zeller2Johannes Zeller3Tracy L. Nero4Tracy L. Nero5Tracy L. Nero6Johanna Klepetko7Steffen U. Eisenhardt8Michael W. Parker9Michael W. Parker10Michael W. Parker11James D. McFadyen12James D. McFadyen13James D. McFadyen14James D. McFadyen15Karlheinz Peter16Karlheinz Peter17Karlheinz Peter18Karlheinz Peter19Department of Cardiometabolic Health, The University of Melbourne, Parkville, VIC, AustraliaBaker Heart and Diabetes Institute, Melbourne, VIC, AustraliaBaker Heart and Diabetes Institute, Melbourne, VIC, AustraliaDepartment of Plastic and Hand Surgery, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, GermanyDepartment of Cardiometabolic Health, The University of Melbourne, Parkville, VIC, AustraliaDepartment of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, VIC, AustraliaAustralian Cancer Research Foundation (ACRF) Rational Drug Discovery Centre, St. Vincent’s Institute of Medical Research, Fitzroy, VIC, AustraliaClinical Laboratory for Bionic Extremity Reconstruction, Department of Plastic, Reconstructive and Aesthetic Surgery, Medical University of Vienna, Vienna, AustriaDepartment of Plastic and Hand Surgery, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, GermanyDepartment of Cardiometabolic Health, The University of Melbourne, Parkville, VIC, AustraliaDepartment of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, VIC, AustraliaAustralian Cancer Research Foundation (ACRF) Rational Drug Discovery Centre, St. Vincent’s Institute of Medical Research, Fitzroy, VIC, AustraliaDepartment of Cardiometabolic Health, The University of Melbourne, Parkville, VIC, AustraliaBaker Heart and Diabetes Institute, Melbourne, VIC, AustraliaDepartment of Clinical Haematology, The Alfred Hospital, Melbourne, VIC, AustraliaThe School of Translational Medicine, Monash University, Melbourne, VIC, AustraliaDepartment of Cardiometabolic Health, The University of Melbourne, Parkville, VIC, AustraliaBaker Heart and Diabetes Institute, Melbourne, VIC, AustraliaThe School of Translational Medicine, Monash University, Melbourne, VIC, AustraliaDepartment of Cardiology, The Alfred Hospital, Melbourne, VIC, AustraliaC-reactive protein (CRP), an acute-phase protein primarily produced by hepatocytes in response to pro-inflammatory cytokines, is a widely used clinical marker for inflammation and tissue damage. In its native state, CRP exists in a stable pentameric form called pCRP. Upon interaction with activated cell membranes, pCRP undergoes a transitional conformation change into activated pCRP (pCRP*) and subsequently fully dissociates into its monomeric subunits (mCRP). pCRP* and mCRP interact with C1q and thereby activate the classical complement system pathway and both exert pro-inflammatory effects on platelets and endothelial cells. Although classically recognized as a marker of acute inflammation, CRP is increasingly implicated in the pathogenesis of protein-misfolding pathologies, notably neurodegenerative diseases and amyloidosis. This review explores the complex interplay between CRP, encompassing its isoforms pCRP, pCRP*, and mCRP, and misfolded proteins, examining the specific contributions to inflammation and neurodegenerative disease pathogenesis. We analyze the clinical significance of variations in CRP levels in patients with protein-misfolding diseases, discuss underlying mechanisms, and highlight potential implications of these findings for drug discovery and therapeutic targeting of CRP.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1612703/fullC-reactive proteinmisfolded proteinsprotein aggregationneurodegenerative diseasesneuroinflammation |
| spellingShingle | Abhishek Roy Abhishek Roy Johannes Zeller Johannes Zeller Tracy L. Nero Tracy L. Nero Tracy L. Nero Johanna Klepetko Steffen U. Eisenhardt Michael W. Parker Michael W. Parker Michael W. Parker James D. McFadyen James D. McFadyen James D. McFadyen James D. McFadyen Karlheinz Peter Karlheinz Peter Karlheinz Peter Karlheinz Peter C-reactive protein: the nexus between inflammation and protein misfolding diseases Frontiers in Immunology C-reactive protein misfolded proteins protein aggregation neurodegenerative diseases neuroinflammation |
| title | C-reactive protein: the nexus between inflammation and protein misfolding diseases |
| title_full | C-reactive protein: the nexus between inflammation and protein misfolding diseases |
| title_fullStr | C-reactive protein: the nexus between inflammation and protein misfolding diseases |
| title_full_unstemmed | C-reactive protein: the nexus between inflammation and protein misfolding diseases |
| title_short | C-reactive protein: the nexus between inflammation and protein misfolding diseases |
| title_sort | c reactive protein the nexus between inflammation and protein misfolding diseases |
| topic | C-reactive protein misfolded proteins protein aggregation neurodegenerative diseases neuroinflammation |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1612703/full |
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