RT Journal Article SR Electronic T1 Protean proteases: at the cutting edge of lung diseases JF European Respiratory Journal JO Eur Respir J FD European Respiratory Society SP 1501200 DO 10.1183/13993003.01200-2015 VO 49 IS 2 A1 Clifford Taggart A1 Marcus A. Mall A1 Gilles Lalmanach A1 Didier Cataldo A1 Andreas Ludwig A1 Sabina Janciauskiene A1 Nicole Heath A1 Silke Meiners A1 Christopher M. Overall A1 Carsten Schultz A1 Boris Turk A1 Keren S. Borensztajn YR 2017 UL http://erj.ersjournals.com/content/49/2/1501200.abstract AB 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