Serpins as therapeutics--a potential biologic source for unique protein-based therapeutics.

摘要

Serine proteinase inhibitors, termed serpins, are a surprisingly prevalent class of regulatory proteins found naturally expressed throughout the human body and in species from microbes to horseshoe crabs and to mammals. Serpinsregulate central serine protease enzyme cascades responsible for clotting, bleeding, immune, endocrine, neurotrophic, and a diverse array of many other pathways. For such a widely disseminated regulatory, there is often a lack of appreciation for theserpins as a class of regulatory proteins. Serpins are also frequently unremarked despite thepotential profound effect on numerous functions. While often unnoticed, the marked efficacy of serpins as a biological class of regulators is now becoming recognized as a potential new therapeutic approach to treatment of diseases where the serine protease pathways have become unbalanced. Of even greater interest is the finding that there is frequent interaction between the proteases and serpins in regulatory pathways and disease states suggesting that there is cross talk between various acute response pathways that is shared throughout the human body. Certainly the thrombotic and thrombolytic pathways have extensive interactions with the inflammatory and apoptotic response systems