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

Engrailed Homeoprotein Protects Mesencephalic Dopaminergic Neurons from Oxidative Stress.

Author information

1
Centre for Interdisciplinary Research in Biology (CIRB), Labex Memolife, CNRS UMR 7241/INSERM U1050, Collège de France, 11 place Marcelin Berthelot, 75231 Paris Cedex 05, France.
2
Centre for Interdisciplinary Research in Biology (CIRB), Labex Memolife, CNRS UMR 7241/INSERM U1050, Collège de France, 11 place Marcelin Berthelot, 75231 Paris Cedex 05, France. Electronic address: alain.prochiantz@college-de-france.fr.

Abstract

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.

PMID:
26411690
PMCID:
PMC5066840
DOI:
10.1016/j.celrep.2015.08.076
[Indexed for MEDLINE]
Free PMC Article

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