Cited by 150Parkinson's Disease Mechanisms and TreatmentsNuclear Receptors and SignalingNeurological disorders and treatments

Engrailed protects mouse midbrain dopaminergic neurons against mitochondrial complex I insults

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Alvarez-Fischer, Daniel, Fuchs, Julia, Castagner, François, Stettler, Olivier, Massiani-Beaudoin, Olivia, Moya, Kenneth L, Bouillot, Colette, Oertel, Wolfgang H +5 more·2011·Nature Neuroscience

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 α-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.

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Crossref · 10.1038/nn.2916

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  • In dopaminergic neurons and retinal ganglion cell growth cones, translation of nuclear-encoded mitochondrial mRNAs commonly occurs after homeoprotein capture.

    “Indeed, translation of nuclear-encoded mitochondrial mRNAs commonly follows homeoprotein capture by dopaminergic neurons or retinal ganglion cell growth cones (Alvarez-Fischer et al., 2011; Stettler et al., 2012; Yoon et al., 2012).”

    From Choroid-Plexus-Derived Otx2 Homeoprotein Constrains Adult Cortical Plasticity (2013) · cites this paper as Alvarez-Fischer et al., 2011

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Authors
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.
Affiliations
  • Centre National de la Recherche Scientifique (FR)
  • Philipps University of Marburg (DE)
  • Inserm (FR)
  • Institut Curie (FR)
Corresponding author
  • Joshi, Rajiv L
  • Hartmann, Andreas
  • Prochiantz, Alain
Venue
Nature Neuroscience
Published
2011-09-04
Volume
14
Issue
10
Pages
1260-1266
ISSN
  • 1097-6256 (ISSN-L)
  • 1546-1726
OpenAlex
W2034104365
Cited by
150
References
51
Citations by year
2026: 5 · 2025: 8 · 2024: 9 · 2023: 9 · 2022: 9 · 2021: 7 · 2020: 10 · 2019: 13 · 2018: 9 · 2017: 10 · 2016: 7 · 2015: 15 · 2014: 13 · 2013: 13 · 2012: 11
FWCI
7.91
Type
journal article
Language
en
Open access
Locations
  • Nature Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, other-oa)
  • HAL Portal Artxiker (Hindustan Aeronautics Limited (India)) (submittedVersion)
  • Oskar-Bordeaux (Universite de Bordeaux) (submittedVersion)
  • Trinity's Access to Research Output (TARA) (Trinity College Dublin) (submittedVersion)
Topics
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
  • Health Sciences › Medicine › Neurology › Neurological disorders and treatments
Keywords
EN1, Engrailed-2, homeodomain transcription factor, midbrain dopaminergic neurons, Parkinson's disease, MPTP-induced neurotoxicity, mitochondrial complex I, NDUFS1, NDUFS3, neuronal survival, substantia nigra pars compacta, 6-hydroxydopamine, striatal dopamine, neuroprotection
MeSH terms
Engrailed 2 Protein, Animals, Cell Count, Cells, Cultured, Chromatography, High Pressure Liquid, Dopamine, Embryo, Mammalian, Male, Mesencephalon, Mice, Inbred C57BL, Mice, Transgenic, NADH Dehydrogenase, Nerve Tissue Proteins, Neurons, Neurotoxins, Nitro Compounds, Propionates, Rotenone, Stereotyped Behavior, Tyrosine 3-Monooxygenase, Dizocilpine Maleate, Oxidopamine, Homeodomain Proteins, RNA, Small Interfering, Electron Transport Chain Complex Proteins, Dopamine Plasma Membrane Transport Proteins, Mice, alpha-Synuclein, In Vitro Techniques

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