Engrailed protects mouse midbrain dopaminergic neurons against mitochondrial complex i insults

Daniel Alvarez-Fischer, Julia Fuchs, Fraņois Castagner, Olivier Stettler, Olivia Massiani-Beaudoin, Kenneth L. Moya, Colette Bouillot, Wolfgang H. Oertel, Anne Lombès, Wolfgang Faigle, Rajiv L. Joshi, Andreas Hartmann, Alain Prochiantz*

*Corresponding author for this work
64 Citations (Scopus)


Mice heterozygous for the homeobox gene Engrailed-1 (En1) display progressive loss of mesencephalic dopaminergic (mDA) neurons. We report that exogenous Engrailed-1 and Engrailed-2 (collectively Engrailed) protect mDA neurons from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a mitochondrial complex I toxin used to model Parkinson's disease in animals. Engrailed enhances the translation of nuclearly encoded mRNAs for two key complex I subunits, Ndufs1 and Ndufs3, and increases complex I activity. Accordingly, in vivo protection against MPTP by Engrailed is antagonized by Ndufs1 small interfering RNA. An association between Engrailed and complex I is further confirmed by the reduced expression of Ndufs1 and Ndufs3 in the substantia nigra pars compacta of En1 heterozygous mice. Engrailed also confers in vivo protection against 6-hydroxydopamine and Î ±-synuclein- A30P. Finally, the unilateral infusion of Engrailed into the midbrain increases striatal dopamine content, resulting in contralateral amphetamine-induced turning. Therefore, Engrailed is both a survival factor for adult mDA neurons and a regulator of their physiological activity.

Original languageEnglish
JournalNature Neuroscience
Issue number10
Pages (from-to)1260-1266
Number of pages7
Publication statusPublished - 01.10.2011


Dive into the research topics of 'Engrailed protects mouse midbrain dopaminergic neurons against mitochondrial complex i insults'. Together they form a unique fingerprint.

Cite this