Chemoattractant Family Related Drug Discovery Products
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Chemerin is an adipokine that produces insulin resistance by the mechanism of inflammation in adipose tissue however these are yet unknown. A high concentration of chemerin in humans is seen as a sign of inflammation in type 2 diabetes mellitus, insulin resistance, obesity, and other conditions. Chemerin is one of the novel adipokines that is proposed to be associated with elevated cancer risk and mortality despite its role in the advancement of insulin resistance.
Fig.1 Overview of the chemerin receptors. (De Henau, 2016)
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Overview of Chemoattractant Family
Chemerin suppresses cAMP synthesis and stimulates phospholipase C activation, IP3 release, calcium mobilization, as well as activation of the PI3K and MAPK pathways in cells expressing CMKLR1, which is related to the Gi/o family of G proteins. It is also known that chemerin stimulates β-arrestin2 to be recruited to CMKLR1, although it is unknown whether this recruitment is unrelated to G protein activation. Chemerin encourages the chemotaxis of leukocyte populations, such as dendritic cells, macrophages, and natural killer cells, that express CMKLR1.
CMKLR2 is the closest homolog of CMKLR1, with which it shares a sequence that is more than 40% identical. A few cell types, including Leydig cells and granulosa cells, as well as the central nervous system, skin, and adipose tissue have been found to express CMKLR2. Although it has been demonstrated that chemerin binding to CMKLR2 weakly activates calcium mobilization in recombinant cell lines, it is still unknown if CMKLR2 initiates signaling cascades in natural contexts. It is possible that CMKLR2 is a scavenger receptor that regulates extracellular chemerin levels because chemerin binding to it causes a fast down-regulation of that receptor.
Chemoattractant Family Drug Discovery
Chemerin may be a predictive biomarker for a variety of disorders, according to mounting data. Furthermore, the creation of pharmacological options that target chemerin and its receptors is advantageous in the management of metabolic syndrome and obesity. To clarify the application of chemerin in routine clinical practice, more study is required. According to a growing body of research, treating disorders other than those caused by obesity may benefit from the effect on chemerin or its receptors.
Reference
- De Henau, O.; et al. Signaling properties of chemerin receptors CMKLR1, GPR1 and CCRL2. PloS one. 2016, 11(10): e0164179.
