Pathogenic Role of Serine Protease HtrA2/Omi in Neurodegenerative Diseases

Curr Protein Pept Sci. 2017;18(7):746-757. doi: 10.2174/1389203717666160311115750.

Abstract

High-temperature-requirement A2 (HtrA2)/Omi/PARK13 is a serine protease with extensive homology to the Escherichia coli HtrAs that are required for bacterial survival at high temperatures. The HtrA2 protein is a key modulator of mitochondrial molecular quality control but under stressful conditions it is released into the cytosol, where it promotes cell death by various pathways, including caspase-dependent pathway and ER stress-mediated apoptosis. Recently, the HtrA2 protein has received great attention for its potential role in neurodegeneration. Here, we review the current knowledge and pathophysiological functions of the HtrA2 protein in neurodegenerative disorders such as Parkinson's and Alzheimer's disease.

Keywords: Alzheimer's disease; HtrA2; HtrA2 interacting proteins; Parkinson’s disease; apoptosis; mitochondria; protein quality control.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / enzymology
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / pathology
  • Caspases / genetics
  • Caspases / metabolism
  • Catalytic Domain
  • Cell Death
  • Endoplasmic Reticulum Stress / genetics*
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism
  • High-Temperature Requirement A Serine Peptidase 2
  • Humans
  • Mitochondria / enzymology*
  • Mitochondria / pathology
  • Mitochondrial Proteins / genetics*
  • Mitochondrial Proteins / metabolism
  • Parkinson Disease / enzymology
  • Parkinson Disease / genetics*
  • Parkinson Disease / pathology
  • Proteolysis
  • Sequence Homology, Amino Acid
  • Serine Endopeptidases / genetics*
  • Serine Endopeptidases / metabolism
  • Substrate Specificity

Substances

  • Escherichia coli Proteins
  • Mitochondrial Proteins
  • Serine Endopeptidases
  • HTRA2 protein, human
  • High-Temperature Requirement A Serine Peptidase 2
  • Caspases