Interplay between HTRA1 and classical signalling pathways in organogenesis and diseases

The high temperature requirement factor A1 (HTRA1) is a serine protease which modulates an array of signalling pathways driving basal biological processes. HTRA1 plays a significant role in cell proliferation, migration and fate determination, in addition to controlling protein aggregates through refolding, translocation or degradation. The mutation of HTRA1 has been implicated in a plethora of disorders and this has also led to its growing interest as drug therapy target. This review details the involvement of HTRA1 in certain signalling pathways, namely the transforming growth factor beta (TGF-β), canonical Wingless/Integrated (WNT) and NOTCH signalling pathways during organogenesis and various disease pathogenesis such as preeclampsia, age-related macular degeneration (AMD), small vessel disease and cancer. We have also explored possible avenues of exploiting the serine proteases for therapeutic management of these disorders.