title: Dissecting the role of Engrailed in adult dopaminergic neurons--Insights into Parkinson disease pathogenesis.
abstract: The homeoprotein Engrailed (Engrailed-1/Engrailed-2, collectively En1/2) is not only a survival factor for mesencephalic dopaminergic (mDA) neurons during development, but continues to exert neuroprotective and physiological functions in adult mDA neurons. Loss of one En1 allele in the mouse leads to progressive demise of mDA neurons in the ventral midbrain starting from 6 weeks of age. These mice also develop Parkinson disease-like motor and non-motor symptoms. The characterization of En1 heterozygous mice have revealed striking parallels to central mechanisms of Parkinson disease pathogenesis, mainly related to mitochondrial dysfunction and retrograde degeneration. Thanks to the ability of homeoproteins to transduce cells, En1/2 proteins have also been used to protect mDA neurons in various experimental models of Parkinson disease. This neuroprotection is partly linked to the ability of En1/2 to regulate the translation of certain nuclear-encoded mitochondrial mRNAs for complex I subunits. Other transcription factors that govern mDA neuron development (e.g. Foxa1/2, Lmx1a/b, Nurr1, Otx2, Pitx3) also continue to function for the survival and maintenance of mDA neurons in the adult and act through partially overlapping but also diverse mechanisms.
authors.affiliation: Center 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.
authors.forename: Hocine
authors.initials: H
authors.lastname: Rekaik
authors.affiliation: Center 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.
authors.forename: François-Xavier
authors.initials: FX
authors.lastname: Blaudin de Thé
authors.affiliation: Center 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.
authors.forename: Alain
authors.initials: A
authors.lastname: Prochiantz
authors.affiliation: Center 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: julia.fuchs@college-de-france.fr.
authors.forename: Julia
authors.initials: J
authors.lastname: Fuchs
authors.affiliation: Center 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: rajiv.joshi@college-de-france.fr.
authors.forename: Rajiv L
authors.initials: RL
authors.lastname: Joshi
mesh_terms: D000818:Animals; D059290:Dopaminergic Neurons / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000502:physiology*; D006801:Humans; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000502:physiology*; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology; D000099266:Engrailed 2 Protein
chemical_list: D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D000099266:Engrailed 2 Protein; C080330:En1 protein, mouse
keywords: Dopaminergic neuron; Engrailed; Homeoprotein; Mitochondria; Parkinson disease; Retrograde degeneration; Substantia nigra pars compacta