Targeting STOX1 in the therapy of preeclampsia

Expert Opin Ther Targets. 2016 Dec;20(12):1433-1443. doi: 10.1080/14728222.2016.1253682. Epub 2016 Nov 8.

Abstract

Preeclampsia is a major pregnancy disease, explained partly by genetic predispositions. STOX1, a transcription factor discovered in 2005, was the first gene directly associated with genetic forms of the disease. Alterations of STOX1 expression as well as STOX1 variants have also been associated to Alzheimer's disease. These observations make of this gene a putative therapeutic target. Area covered: Two major isoforms (STOX1A and STOX1B) are encoded by the gene and are theoretically able to compete for the same binding site, while only the most complete (STOX1A) is supposed to be able to activate gene expression. This makes the ratio between STOX1A and STOX1B as well as their position inside the cell (nucleus or cytoplasm) crucial to understand how STOX1 functions. STOX1 appears to have multiple gene targets, especially in pathways connected to inflammation, oxidative stress, and cell cycle. Expert opinion: STOX1-directed therapies, could be directed either towards its targets (genes or pathways), or directly at STOX1. For this the addressing of STOX1 to various cell compartments could theoretically be modified; also it could be possible of altering the balance between the two isoforms, through selectively inhibiting one of them, possibly improving the outcomes in severe preeclampsia.

Keywords: Preeclampsia; alzheimer’s disease; gene expression regulation; inflammation; oxidative stress; placenta.

Publication types

  • Review

MeSH terms

  • Animals
  • Binding, Competitive
  • Carrier Proteins / genetics*
  • Cell Cycle / genetics
  • Female
  • Gene Expression Regulation
  • Genetic Predisposition to Disease
  • Humans
  • Inflammation / genetics
  • Molecular Targeted Therapy*
  • Oxidative Stress / genetics
  • Pre-Eclampsia / genetics
  • Pre-Eclampsia / therapy*
  • Pregnancy
  • Protein Isoforms

Substances

  • Carrier Proteins
  • Protein Isoforms
  • STOX1 protein, human