Protein biomarkers in cystic fibrosis research where next 英文参考文献.docVIP

Pattison and Elborn Genome Medicine 2010,2:88 /content/2/12/88 RE VIE W Protein biomarkers in cystic brosis research: where next? Sally H Pattison and J Stuart Elborn* Abstract Cystic brosis is one of the most common life-limiting inherited disorders. Its clinical impact manifests chiey in the lung, pancreas, gastrointestinal tract and sweat glands, with lung disease typically being most detrimental to health. The median age for survival has increased dramatically over the past decades, largely thanks to advances in understanding of the mechanisms and consequences of disease, leading to the development of better therapies and treatment regimes. The discovery of dysregulated protein biomarkers linked to cystic brosis has contributed considerably to this end. This article outlines clinical trials targeting known protein biomarkers, and the current and future contributions of proteomic techniques to cystic brosis research. The treatments described range from those designed to provide functional copies of the mutant protein responsible for cystic brosis, to others addressing the associated symptoms of chronic inammation. Preclinical research has employed proteomics to help elucidate pathways and processes implicated in disease that might present opportunities for therapy or prognosis. Global analyses of cystic brosis have detected the dierential expression of proteins involved in inammation, proteolytic activity and oxidative stress, which are recognized symptoms of the cystic brosis phenotype. The dysregulation of other processes, such as the complement and mitochondrial systems, has also been implicated. A number of studies have focused specically on proteins that interact with the cystic brosis protein, with the goal of restoring its normal proteostasis. Consequently, proteins involved in synthesis, folding, degradation, translocation and localization of the protein have been identied as potential therapeutic targets. Cystic brosis patients are prone to lung