哮喘联盟

   摘要
   对炎症细胞和分子生物学以及气道平滑肌收缩性研究的显著进展提示数个哮喘治疗的潜在靶点。针对包括苦味受体(TAS2R)激动剂和前列腺素EP4受体激动剂在内的G-蛋白成对受体的新药能引起ASM舒张。尽管有新的PDE抑制剂出现，一种新的PKA靶蛋白——HSP20——通过肌动蛋白解聚介导平滑肌舒张，cAMP/PKA通路仍然是有效的药物靶点。平滑肌舒张也可以由RhoA/Rho激酶通路抑制剂通过抑制肌球蛋白轻链磷酸化和肌动蛋白解聚来介导。控制气道核染色质重构和RNA-诱导基因沉默的后生靶向过程同样是潜在的哮喘治疗位点。进一步的研究将确定能够抑制平滑肌收缩和/或抑制或逆转气道阻塞性重构的物质。
 

（林江涛 审校）
CurrOpinPharmacol.2013Apr29.pii:S1471-4892(13)00051-9.doi:10.1016/j.coph.2013.04.002. [Epub ahead of print]

 

Emerging targets for novel therapy of asthma.

Gerthoffer WT, Solway J, Camoretti-Mercado B.

Abstract
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 (GPCRs) including bitter taste receptors (TAS2R) agonists and prostaglandin EP4 receptor agonists elicit ASM 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.

CurrOpinPharmacol.2013Apr29.pii:S1471-4892(13)00051-9.doi:10.1016/j.coph.2013.04.002. [Epub ahead of print]