Roles of PTEN with DNA Repair in Parkinson's Disease

Int J Mol Sci. 2016 Jun 15;17(6):954. doi: 10.3390/ijms17060954.

Abstract

Oxidative stress is considered to play key roles in aging and pathogenesis of many neurodegenerative diseases such as Parkinson's disease, which could bring DNA damage by cells. The DNA damage may lead to the cell apoptosis, which could contribute to the degeneration of neuronal tissues. Recent evidence suggests that PTEN (phosphatase and tensin homolog on chromosome 10) may be involved in the pathophysiology of the neurodegenerative disorders. Since PTEN expression appears to be one dominant determinant of the neuronal cell death, PTEN should be a potential molecular target of novel therapeutic strategies against Parkinson's disease. In addition, defects in DNA damage response and DNA repair are often associated with modulation of hormone signaling pathways. Especially, many observations imply a role for estrogen in a regulation of the DNA repair action. In the present review, we have attempted to summarize the function of DNA repair molecules at a viewpoint of the PTEN signaling pathway and the hormone related functional modulation of cells, providing a broad interpretation on the molecular mechanisms for treatment of Parkinson's disease. Particular attention will be paid to the mechanisms proposed to explain the health effects of food ingredients against Parkinson's disease related to reduce oxidative stress for an efficient therapeutic intervention.

Keywords: BRCA1; DNA repair; PTEN; Parkinson’s disease; ROS; estrogen; oxidative stress.

Publication types

  • Review

MeSH terms

  • Animals
  • BRCA1 Protein / genetics
  • BRCA1 Protein / metabolism
  • Cell Survival / genetics
  • DNA Damage
  • DNA Repair*
  • Diet
  • Estrogens / metabolism
  • Humans
  • Nerve Degeneration / genetics
  • Nerve Degeneration / metabolism
  • Neurodegenerative Diseases / genetics
  • Neurodegenerative Diseases / metabolism
  • Neurodegenerative Diseases / pathology
  • Oxidative Stress
  • PTEN Phosphohydrolase / metabolism*
  • Parkinson Disease / genetics*
  • Parkinson Disease / metabolism*
  • Parkinson Disease / pathology
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Reactive Oxygen Species / metabolism
  • Receptors, Estrogen / metabolism
  • Signal Transduction

Substances

  • BRCA1 Protein
  • Estrogens
  • Reactive Oxygen Species
  • Receptors, Estrogen
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • PTEN Phosphohydrolase