TY - JOUR T1 - Protean proteases: at the cutting edge of lung diseases JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.01200-2015 VL - 49 IS - 2 SP - 1501200 AU - Clifford Taggart AU - Marcus A. Mall AU - Gilles Lalmanach AU - Didier Cataldo AU - Andreas Ludwig AU - Sabina Janciauskiene AU - Nicole Heath AU - Silke Meiners AU - Christopher M. Overall AU - Carsten Schultz AU - Boris Turk AU - Keren S. Borensztajn Y1 - 2017/02/01 UR - http://erj.ersjournals.com/content/49/2/1501200.abstract N2 - Proteases were traditionally viewed as mere protein-degrading enzymes with a very restricted spectrum of substrates. A major expansion in protease research has uncovered a variety of novel substrates, and it is now evident that proteases are critical pleiotropic actors orchestrating pathophysiological processes. Recent findings evidenced that the net proteolytic activity also relies upon interconnections between different protease and protease inhibitor families in the protease web.In this review, we provide an overview of these novel concepts with a particular focus on pulmonary pathophysiology. We describe the emerging roles of several protease families including cysteine and serine proteases.The complexity of the protease web is exemplified in the light of multidimensional regulation of serine protease activity by matrix metalloproteases through cognate serine protease inhibitor processing. Finally, we will highlight how deregulated protease activity during pulmonary pathogenesis may be exploited for diagnosis/prognosis purposes, and utilised as a therapeutic tool using nanotechnologies.Considering proteases as part of an integrative biology perspective may pave the way for the development of new therapeutic targets to treat pulmonary diseases related to intrinsic protease deregulation.Emergence of integrative protease biology offers new insights into the fundamental mechanisms of lung pathophysiology http://ow.ly/a7XH3077Muu ER -