pCRP-mCRP dissociation mechanisms as potential targets for the development of small-molecule anti-inflammatory chemotherapeutics
Caprio, Vittorio (Manchester Metropolitan University)
Badimon, Lina (Institut d'Investigació Biomèdica Sant Pau)
Di Napoli, Mario (Ospedale San Camillo de Lellis)
Fang, Wen-Hui (Manchester Metropolitan University)
Ferris, Glenn R. (Manchester Metropolitan University)
Guo, Baoqiang (Weifang Medical University)
Iemma, Rocco S. (Manchester Metropolitan University)
Liu, Donghui (University of Medicine and Pharmacy)
Zeinolabediny, Yasmin (University of Medicine and Pharmacy)
Slevin, Mark (University of Medicine and Pharmacy)
Universitat Autònoma de Barcelona

Data:	2018
Resum:	Circulating C-reactive protein (CRP) is a key acute-phase protein and one of the main clinical biomarkers for inflammation and infection. CRP is an important upstream mediator of inflammation and is associated with the onset of a number of important disease states including cardiovascular disease and neurodegenerative disorders such as Alzheimer's disease. This pentraxin exerts pro-inflammatory properties via dissociation of the pentamer (pCRP) to a monomeric form (mCRP). This dissociation is induced by binding of pCRP to cell surface phosphocholine residues exposed by the action of phospholipase A (PLA). Given the association of CRP with the onset of a range of serious disease states this CRP dissociation process is a tempting drug target for the development of novel small-molecule therapeutics. This review will discuss potential targets for chemotherapeutic intervention elucidated during studies of CRP-mediated inflammation and provide an up-to-date summary of the development of small molecules, not only targeted directly at inhibiting conversion of pCRP to mCRP, but also those developed for activity against PLA, given the key role of this enzyme in the activation of CRP.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	CRP ; Inflammation ; Chemotherapy ; Phospholipid ; Phospholipase
Publicat a:	Frontiers in immunology, Vol. 9 Núm. MAY (28 2018) , p. 1089, ISSN 1664-3224

DOI: 10.3389/fimmu.2018.01089
PMID: 29892284

7 p, 979.4 KB

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