| First Author | Alvarez-Fischer D | Year | 2011 |
| Journal | Nat Neurosci | Volume | 14 |
| Issue | 10 | Pages | 1260-6 |
| PubMed ID | 21892157 | Mgi Jnum | J:179779 |
| Mgi Id | MGI:5303040 | Doi | 10.1038/nn.2916 |
| Citation | Alvarez-Fischer D, et al. (2011) Engrailed protects mouse midbrain dopaminergic neurons against mitochondrial complex I insults. Nat Neurosci 14(10):1260-6 |
| abstractText | 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 alpha-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. |
