Emerging targets for novel therapy of asthma.
Emerging targets for novel therapy of asthma.
复制标题
DOI：
10.1016/j.coph.2013.04.002
复制
发表时间：
2013-06
影响因子：
4
通讯作者：
Camoretti-Mercado B
中科院分区：
文献类型：
--
作者：
Gerthoffer WT;Solway J;Camoretti-Mercado B
在了解炎症和气道平滑肌(ASM)收缩的细胞和分子生物学方面取得的重大进展已经确定了几个潜在的哮喘治疗新靶点。针对G蛋白偶联受体(GPCR)的新药物，包括苦味受体(TAS2R)激动剂和前列腺素EP4受体激动剂，可诱导气道平滑肌松弛。随着新的PDE抑制剂和一种新的PKA靶蛋白HSP20的出现，cAMP/PKA途径仍然是一个有希望的药物靶点，HSP20通过肌动蛋白解聚介导平滑肌松弛。通过抑制肌球蛋白轻链磷酸化和肌动蛋白解聚，RhoA/Rho激酶通路的抑制剂也可以引起平滑肌松弛。靶向控制染色质重塑和RNA诱导的呼吸道细胞基因沉默的表观遗传过程也为新型哮喘治疗提供了巨大的潜力。进一步的研究可能会发现抑制平滑肌收缩和/或抑制或逆转阻塞性呼吸道重塑的药物。
Significant advances in understanding the cell and molecular biology of inflammation and airway smooth muscle (ASM) contractility have identified several potential novel targets for therapies of asthma. New agents targeting G-protein coupled receptors (GPCR) including bitter taste receptors (TAS2R) agonists and prostaglandin EP4 receptor agonists elicit airway smooth muscle relaxation. The cAMP/PKA pathway continues to be a promising drug target with the emergence of new PDE inhibitors and a novel PKA target protein, HSP20, which mediates smooth muscle relaxation via actin depolymerization. Smooth muscle relaxation can also be elicited by inhibitors of the RhoA/Rho kinase pathway via inhibition of myosin light chain phosphorylation and actin depolymerization. Targeting epigenetic processes that control chromatin remodeling and RNA-induced gene silencing in airway cells also holds great potential for novel asthma therapy. Further investigation may identify agents that inhibit smooth muscle contraction and/or restrain or reverse obstructive remodeling of the airways.
登录
查看更多内容
气道平滑肌上的苦味受体通过局部钙信号传导和反向阻塞来支气管扩张。
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
5
作者：
Ito, Satoru;Kume, Hiroaki;Naruse, Keiji
通讯作者：
Naruse, Keiji
DOI：
10.1152/ajplung.00235.2007
发表时间：
2008-01-01
影响因子：
4.9
作者：
Komalavilas, Padmini;Penn, Raymond B.;Brophy, Colleen M.
通讯作者：
Brophy, Colleen M.
影响因子：
3.2
作者：
Benyahia, C.;Gomez, I.;Norel, X.
通讯作者：
Norel, X.
影响因子：
4.8
作者：
Dreiza, CM;Brophy, CM;Panitch, A
通讯作者：
Panitch, A