Targeting C-Reactive Protein in Inflammatory Disease by Preventing Conformational Changes

Area of Science:

• Biochemistry
• Immunology
• Molecular Biology

Background:

• C-reactive protein (CRP) is a clinical inflammation marker.
• Emerging evidence suggests CRP also actively mediates inflammation.
• CRP exists in distinct conformations with opposing inflammatory roles.

Purpose of the Study:

• To review the literature on CRP's structural changes and inflammatory potential.
• To explore the role of pentameric CRP (pCRP) dissociation into monomeric CRP (mCRP) in inflammation.
• To discuss therapeutic strategies targeting CRP conformation in inflammatory diseases.

Main Methods:

• Literature review of current research on CRP structure and function.
• Analysis of studies using conformation-specific antibodies to identify CRP forms in inflamed tissues.
• Examination of findings on pCRP dissociation mechanisms.

Main Results:

• Native pentameric CRP (pCRP) converts to pro-inflammatory monomeric CRP (mCRP).
• pCRP dissociation occurs on activated platelets and cells, amplifying inflammation.
• mCRP conformation is found in CRP deposits within inflamed tissues.
• This mechanism contributes to inflammatory conditions like atherosclerosis and ischemia/reperfusion injury.

Conclusions:

• The dissociation of pCRP to mCRP is a key mechanism amplifying inflammation.
• Targeting pCRP dissociation presents a therapeutic strategy for inflammatory diseases.
• Development of compounds like 1,6-bis(phosphocholine)-hexane (1,6-bis PC) is crucial for future research.