Recent patents on Rho signaling pathway as therapeutic target for cardiovascular diseases.
Rho protein represents a family of small GTP binding proteins that are involved in many important cellular functions including cell proliferation, migration and cytoskeletal reorganization. Rho protein is activated by GTP binding and is inactivated by hydrolyzing GTP to GDP. This process is influenced by variety of physiological and pathophysiological stimuli including growth factors, many vasoactive substances, smoking and mechanic stress or injury. Recent evidence suggest that targeting Rho protein per se or its downstream effector proteins such as Rho kinase or LIM kinase may have therapeutic potential in diseases such as hypertension, angina, myocardiac infarction (MI), atherosclerosis, tumor metastasis and spinal cord injury. Several recent patents have described modalities that regulate the activity of Rho, Rho kinase and LIM kinase as potential therapeutics. In this article, we will review the current knowledge on the cellular functions of Rho signaling pathway and strategies in targeting different components in Rho signaling pathway for human diseases with an emphasis on cardiovascular indications.
Hu
Erding
E
Department of Vascular Biology and Thrombosis, Center of Excellence for Cardiovascular and Urogenital Drug Discovery, GlaxoSmithkline Pharmaceuticals, 709 Swedeland Road, King of Prussia, PA 19406, USA. Erding.Hu@gsk.com
D000818:Animals; D002318:Cardiovascular Diseases / Q000188:drug therapy*; D004730:Endothelium, Vascular / Q000502:physiology; D006801:Humans; D054461:Lim Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors* / Q000502:physiology
D054461:Lim Kinases; D054460:rho-Associated Kinases