Targeting the secretory pathway for anti-inflammatory drug development

Inflammatory diseases are a complex group of disorders involving multiple levels of the immune system and as such present a daunting challenge to understand and treat. Contemporary drug development targets individual cytokines, chemokines, and receptors for which we have some knowledge of their function and regulation. One largely unexplored approach is to modify the inflammatory response via targets within the intracellular secretory pathway. This constitutive pathway is responsible for protein processing and trafficking quality control, and is comprised of the endoplasmic reticulum, the Golgi apparatus, and various post-Golgi organelles such as lysosomes, endosomes, secretory granules, and the plasma membrane. Renewed interest in the secretory system has resulted from our expanding appreciation of the role of post-translational processing in protein function, the myriad of inflammatory and other diseases which arise from defects in the secretory system, and the outcome of drug treatments that utilize elements of this pathway to treat human disease. This review will examine the secretory pathway with particular attention to the phenotypes of diseases which result from disruption of its components, as well as the pharmacological agents that utilize the system to modulate aberrant cellular processes.