Signal peptide peptidase and SPP-like proteases - Possible therapeutic targets?

Mentrup, Torben; Loock, Ann-Christine; Fluhrer, Regina and Schroeder, Bernd (2017): Signal peptide peptidase and SPP-like proteases - Possible therapeutic targets? In: Biochimica et Biophysica Acta-Molecular Cell Research, Vol. 1864, No. 11: pp. 2169-2182

Abstract

Signal peptide peptidase (SPP) and the four homologous SPP-like proteases SPPL2a, SPPL2b, SPPL2c and SPPL3 are GxGD-type intramembrane-cleaving proteases (I-CLIPs). In addition to divergent subcellular localisations, distinct differences in the mechanistic properties and substrate requirements of individual family members have been unravelled. SPP/SPPL proteases employ a catalytic mechanism related to that of the gamma-secretase complex. Nevertheless, differential targeting of SPP/SPPL proteases and gamma-secretase by inhibitors has been demonstrated. Furthermore, also within the SPP/SPPL family significant differences in the sensitivity to currently available inhibitory compounds have been reported. Though far from complete, our knowledge on pathophysiological functions of SPP/SPPL proteases, in particular based on studies in mice, has been significantly increased over the last years. Based on this, inhibition of distinct SPP/SPPL proteases has been proposed as a novel therapeutic concept e.g. for the treatment of autoimmunity and viral or protozoal infections, as we will discuss in this review. This article is part of a Special Issue entitled: Proteolysis as a Regulatory Event in Pathophysiology edited by Stefan Rose-John.

• Item Type: Journal article
• Faculties: Medicine
• Subjects: 600 Technology > 610 Medicine and health
• ISSN: 0167-4889
• Language: English