Engrailed Homeoprotein Protects Mesencephalic Dopaminergic Neurons from Oxidative Stress

Cell Rep. 2015 Oct 13;13(2):242-50. doi: 10.1016/j.celrep.2015.08.076. Epub 2015 Sep 24.


Engrailed homeoproteins are expressed in adult dopaminergic neurons of the substantia nigra. In Engrailed1 heterozygous mice, these neurons start dying at 6 weeks, are more sensitive to oxidative stress, and progressively develop traits similar to those observed following an acute and strong oxidative stress inflected to wild-type neurons. These changes include DNA strand breaks and the modification (intensity and distribution) of several nuclear and nucleolar heterochromatin marks. Engrailed1 and Engrailed2 are biochemically equivalent transducing proteins previously used to antagonize dopaminergic neuron death in Engrailed1 heterozygous mice and in mouse models of Parkinson disease. Accordingly, we show that, following an acute oxidative stress, a single Engrailed2 injection restores all nuclear and nucleolar heterochromatin marks, decreases the number of DNA strand breaks, and protects dopaminergic neurons against apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Apoptosis
  • DNA Damage
  • Dopaminergic Neurons / metabolism*
  • Heterochromatin / genetics
  • Homeodomain Proteins / administration & dosage
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / pharmacology*
  • Infusions, Intraventricular
  • Mice
  • Molecular Sequence Data
  • Nerve Tissue Proteins / administration & dosage
  • Nerve Tissue Proteins / pharmacology*
  • Neuroprotective Agents / administration & dosage
  • Neuroprotective Agents / pharmacology*
  • Oxidative Stress*
  • Substantia Nigra / cytology
  • Substantia Nigra / metabolism*


  • En1 protein, mouse
  • Heterochromatin
  • Homeodomain Proteins
  • Nerve Tissue Proteins
  • Neuroprotective Agents
  • engrailed 2 protein

Associated data

  • GEO/GSE72321