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

doi:10.1038/nn.2916

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^*

^*Korrespondierende/r Autor/-in für diese Arbeit

Klinik für Psychiatrie und Psychotherapie

122 Zitate (Scopus)

Abstract

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.

Originalsprache	Englisch
Zeitschrift	Nature Neuroscience
Jahrgang	14
Ausgabenummer	10
Seiten (von - bis)	1260-1266
Seitenumfang	7
ISSN	1097-6256
DOIs	https://doi.org/10.1038/nn.2916
Publikationsstatus	Veröffentlicht - 01.10.2011

Fördermittel

This work was supported by Agence Nationale pour la Recherche (ANR-06-013-01), the Michael. J. Fox Foundation (MJFF), Fondation de France (Physiopathology of Parkinson disease) and the European Community (FP7 222999, mdDANeurodev project). D.A.-F. was funded by the MJFF, the University Medical Center Giessen and Marburg (UKGM) and the German Academic Exchange Service (DAAD). The CIRB group is part of a Global Research Laboratory (KAIST, South Korea) and a Foundation for Medical Research (FRM) team. J.F. was funded by the German Research Foundation (DFG), the MJFF, FRM and NERF (Neuropôle de Recherche Francilien). A.H. was temporarily supported by INSERM. We thank E. Ipendey for technical help. Confocal imaging and quantification were performed by V. Mignon and B. Saubaméa. We thank the Laboratory of Mass Spectrometry and Proteomics, Institut Curie for assistance. We are indebted to A. Prigent, E. Hirsch, P. Michel and M. Volovitch for intellectual input.

UN SDGs

Dieser Output leistet einen Beitrag zu folgendem(n) Ziel(en) für nachhaltige Entwicklung

SDG 3 – Gesundheit und Wohlergehen
SDG 10 – Weniger Ungleichheiten

Dokumente

10.1038/nn.2916

Weitere Links

Link to publication in Scopus

Zitieren

Alvarez-Fischer, D., Fuchs, J., Castagner, F., Stettler, O., Massiani-Beaudoin, O., Moya, K. L., Bouillot, C., Oertel, W. H., Lombès, A., Faigle, W., Joshi, R. L., Hartmann, A., & Prochiantz, A. (2011). Engrailed protects mouse midbrain dopaminergic neurons against mitochondrial complex i insults. Nature Neuroscience, 14(10), 1260-1266. https://doi.org/10.1038/nn.2916

@article{89c1e308251545b89650d96bf17cc12d,

title = "Engrailed protects mouse midbrain dopaminergic neurons against mitochondrial complex i insults",

abstract = "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 {\^I} ±-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.",

author = "Daniel Alvarez-Fischer and Julia Fuchs and Fraņois Castagner and Olivier Stettler and Olivia Massiani-Beaudoin and Moya, \{Kenneth L.\} and Colette Bouillot and Oertel, \{Wolfgang H.\} and Anne Lomb{\`e}s and Wolfgang Faigle and Joshi, \{Rajiv L.\} and Andreas Hartmann and Alain Prochiantz",

year = "2011",

month = oct,

day = "1",

doi = "10.1038/nn.2916",

language = "English",

volume = "14",

pages = "1260--1266",

journal = "Nature Neuroscience",

issn = "1097-6256",

publisher = "Nature Research",

number = "10",

}

TY - JOUR

T1 - Engrailed protects mouse midbrain dopaminergic neurons against mitochondrial complex i insults

AU - Alvarez-Fischer, Daniel

AU - Fuchs, Julia

AU - Castagner, Fraņois

AU - Stettler, Olivier

AU - Massiani-Beaudoin, Olivia

AU - Moya, Kenneth L.

AU - Bouillot, Colette

AU - Oertel, Wolfgang H.

AU - Lombès, Anne

AU - Faigle, Wolfgang

AU - Joshi, Rajiv L.

AU - Hartmann, Andreas

AU - Prochiantz, Alain

PY - 2011/10/1

Y1 - 2011/10/1

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/80053220669

U2 - 10.1038/nn.2916

DO - 10.1038/nn.2916

M3 - Journal articles

C2 - 21892157

AN - SCOPUS:80053220669

SN - 1097-6256

VL - 14

SP - 1260

EP - 1266

JO - Nature Neuroscience

JF - Nature Neuroscience

IS - 10

ER -

Engrailed protects mouse midbrain dopaminergic neurons against mitochondrial complex i insults

Abstract

Fördermittel

UN SDGs

Dokumente

Weitere Links

Fingerprint

Zitieren