Abstract
Monomeric C-reactive protein (mCRP), once thought to be a figment of the imagination and whose biological activity was ascribed to its sodium azide preservative, has now pronounced itself as a critical molecule playing a direct role in mediating many of the acute and chronic aberrant pathological responses to inflammation. In this focused mini review, we describe the currently attributed pathobiological interactions of mCRP in disease, where its tissue and cellular distribution and deposition have recently been clearly characterized and linked to inflammation and other pathway-associated progression of neurological and cardiovascular complications and deleterious outcomes. and focus upon current opinions as to the diagnostic and prognostic potential of mCRP-plasma circulating protein and define the possible future therapeutics including ongoing research attempting to block CRP dissociation with small molecule inhibitors or prevention of cell surface binding directly using antibodies or modified orphan drug targeting directed towards CRP, inhibiting its cellular interactions and signaling activation. There is no doubt that understanding the full influence of the biological power of mCRP in disease development and outcome will be considered a critical parameter in future stratified treatment.
Highlights
The physiological functions of C-reactive protein (CRP) and the precise mechanisms through which it activates complement, modulates the innate immune system, and opsonizes invading pathogens are fully understood to date [1] and this mini-review will focus on summarizing the emerging pathological indications of its precursor sub-unit-monomeric CRP and discussing the relevant prognostic, diagnostic and therapeutic possibilities of its utilization
CRP has proven itself to be a marker of inflammation but more importantly, an important driver of the process and initiator of signal transduction cascades associated with pathologies linking to neurodegeneration, unstable atherosclerosis and autoimmune conditions amongst others
Modulation of Monomeric C-reactive protein (mCRP) might help protect from development of dementia, stroke and heart disease, mediated by chronic inflammatory-associated tissue damage
Summary
The physiological functions of C-reactive protein (CRP) and the precise mechanisms through which it activates complement, modulates the innate immune system, and opsonizes invading pathogens are fully understood to date [1] and this mini-review will focus on summarizing the emerging pathological indications of its precursor sub-unit-monomeric CRP (mCRP) and discussing the relevant prognostic, diagnostic and therapeutic possibilities of its utilization. Potempa et al eloquently summarized the process in a recent review explaining how the hepatocyte-produced pentameric blood soluble and weakly anti-inflammatory protein becomes converted to an intermediate form that is less soluble and exists as a transitional or modified pCRP bound to cell membrane exposed phosphocholine groups, prior to rapid disulfide bridge breakdown and formation of the monomeric version that is insoluble in the blood and found almost entirely partnered with particulate components, cells and tissues and having significantly higher inflammatory and other bioactive properties [4] This mCRP dissociated form is understood to be capable of directly and actively aggravating perpetuating inflammation at least in part through activation of M1 macrophage phenotype and subsequent expression of cytokines including tumor necrosis factor-alpha (TNF-a) and IL-6, in addition to promoting platelet and platelet-macrophage adhesion and aggregation [5]. Whilst measurement of serum soluble native (high-sensitive) CRP remains valuable for monitoring general levels of inflammation and infection, it is clear that a complete understanding of the pathobiological course of inflammatory disease requires us to assess the footprint of mCRP and consider opportunities to modify its effects and concomitantly protect patients from its deleterious activities
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