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

Publikation: Beitrag in FachzeitschriftÜbersichtsartikel (Review)EingeladenBegutachtung

Beitragende

  • Torben Mentrup - , Institut für Physiologische Chemie, Christian-Albrechts-Universität zu Kiel (CAU) (Autor:in)
  • Ann Christine Loock - , Christian-Albrechts-Universität zu Kiel (CAU) (Autor:in)
  • Regina Fluhrer - , Ludwig-Maximilians-Universität München (LMU), Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) (Autor:in)
  • Bernd Schröder - , Institut für Physiologische Chemie, Christian-Albrechts-Universität zu Kiel (CAU) (Autor:in)

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 γ-secretase complex. Nevertheless, differential targeting of SPP/SPPL proteases and γ-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.

Details

OriginalspracheEnglisch
Seiten (von - bis)2169-2182
Seitenumfang14
FachzeitschriftBiochimica et Biophysica Acta - Molecular Cell Research
Jahrgang1864
Ausgabenummer11
PublikationsstatusVeröffentlicht - Nov. 2017
Peer-Review-StatusJa

Externe IDs

PubMed 28624439

Schlagworte

ASJC Scopus Sachgebiete

Schlagwörter

  • Autoimmunity, ERAD, Intramembrane proteolysis, Signal peptide peptidase, SPPL proteases, γ-Secretase