Development of Inflammatory Immune Response-Related Drugs Based on G Protein-Coupled Receptor Kinase 2
| Autor: | Yuwen Zhang, Dongqian Cui, Chen-Chen Han, Yang Wang, Yifan Li, Yang Ma, Wei Wei, Tingting Luo |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
G-Protein-Coupled Receptor Kinase 2 Physiology G protein-coupled receptor kinase 2 (GRK2) GRK2 inhibitors lcsh:Physiology lcsh:Biochemistry 03 medical and health sciences 0302 clinical medicine Immune system Drug Development Neoplasms Humans Medicine Disease lcsh:QD415-436 Lymphocytes Kinase activity Receptor Protein Kinase Inhibitors Inflammation Regulation of gene expression G protein-coupled receptor kinase lcsh:QP1-981 biology business.industry Kinase Beta adrenergic receptor kinase Soft regulation of inflammatory immune responses (SRIIR) 030104 developmental biology Cardiovascular Diseases Inflammatory immune response (IIR) Cancer research biology.protein Cytokine secretion business 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | Cellular Physiology and Biochemistry, Vol 51, Iss 2, Pp 729-745 (2018) |
| ISSN: | 1421-9778 1015-8987 |
| DOI: | 10.1159/000495329 |
| Popis: | G protein-coupled receptor kinase 2 (GRK2), as a vital Ser/Thr kinase, is an important regulatory protein in the inflammatory immune response (IIR) by maintaining the balance between the function of inflammatory immune cells and non-conventional inflammatory immune cells and regulating inflammatory immune cell infiltration, inflammatory cytokine secretion, and the signaling associated with endothelial function. However, the imbalance of GRK2 expression and activity plays an important role in the development of IIR-related diseases, such as hypertension, heart failure, Alzheimer’s disease, type 2 diabetes mellitus, insulin resistance, rheumatoid arthritis, thyroid cancer, multiple sclerosis, and liver cancer. Small molecule GRK2 inhibitors, including balanol, Takeda inhibitors, paroxetine and derivatives, M119 and gallein, peptides, RNA aptamers, Raf kinase inhibitory protein, and microRNAs, that can directly inhibit GRK2 kinase activity have been identified by different strategies. This review discusses recent progress in one of the hallmark molecular abnormalities of GRK2 in IIR-related diseases and explores the soft regulation of IIR by innovative drugs reducing the excessive activity of GRK2 to basal levels, without damaging normal physiological function, to ameliorate inflammatory disorders. |
| Databáze: | OpenAIRE |
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