Dissecting the role of Engrailed in adult dopaminergic neurons: Insights into Parkinson disease pathogenesis
Identifieur interne : 000225 ( Pmc/Checkpoint ); précédent : 000224; suivant : 000226Dissecting the role of Engrailed in adult dopaminergic neurons: Insights into Parkinson disease pathogenesis
Auteurs : Hocine Rekaik ; François-Xavier Blaudin De Thé ; Alain Prochiantz ; Julia Fuchs ; Rajiv L. JoshiSource :
- FEBS letters [ 0014-5793 ] ; 2015.
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.
Url:
DOI: 10.1016/j.febslet.2015.10.002
PubMed: 26459030
PubMed Central: 5066838
Affiliations:
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<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">0155157</journal-id><journal-id journal-id-type="pubmed-jr-id">3696</journal-id><journal-id journal-id-type="nlm-ta">FEBS Lett</journal-id><journal-id journal-id-type="iso-abbrev">FEBS Lett.</journal-id><journal-title-group><journal-title>FEBS letters</journal-title></journal-title-group><issn pub-type="ppub">0014-5793</issn><issn pub-type="epub">1873-3468</issn></journal-meta><article-meta><article-id pub-id-type="pmid">26459030</article-id><article-id pub-id-type="pmc">5066838</article-id><article-id pub-id-type="doi">10.1016/j.febslet.2015.10.002</article-id><article-id pub-id-type="manuscript">EMS70138</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Dissecting the role of Engrailed in adult dopaminergic neurons: Insights into Parkinson disease pathogenesis</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Rekaik</surname><given-names>Hocine</given-names></name></contrib><contrib contrib-type="author"><name><surname>Blaudin de Thé</surname><given-names>François-Xavier</given-names></name></contrib><contrib contrib-type="author"><name><surname>Prochiantz</surname><given-names>Alain</given-names></name></contrib><contrib contrib-type="author"><name><surname>Fuchs</surname><given-names>Julia</given-names></name><xref ref-type="corresp" rid="CR1">*</xref></contrib><contrib contrib-type="author"><name><surname>Joshi</surname><given-names>Rajiv L.</given-names></name><xref ref-type="corresp" rid="CR1">*</xref></contrib><aff id="A1">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</aff></contrib-group><author-notes><corresp id="CR1"><label>*</label>Corresponding author. Address : Development and Neuropharmacology, Center for Interdisciplinary Research in Biology (CIRB), CNRS UMR 7241, INSERM U1050, Collège de France, 11 Place Marcelin Berthelot, 75005 Paris France. Fax : +33 1 44 27 15 65. <email>julia.fuchs@college-de-france.fr</email> (J. Fuchs), <email>rajiv.joshi@college-de-france.fr</email> (R.L. Joshi).</corresp></author-notes><pub-date pub-type="nihms-submitted"><day>12</day><month>10</month><year>2016</year></pub-date><pub-date pub-type="epub"><day>13</day><month>10</month><year>2015</year></pub-date><pub-date pub-type="ppub"><day>21</day><month>12</month><year>2015</year></pub-date><pub-date pub-type="pmc-release"><day>17</day><month>10</month><year>2016</year></pub-date><volume>589</volume><issue>24 Pt A</issue><fpage>3786</fpage><lpage>3794</lpage><pmc-comment>elocation-id from pubmed: 10.1016/j.febslet.2015.10.002</pmc-comment>
<abstract><p id="P1">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.</p></abstract><kwd-group><kwd>Dopaminergic neurons</kwd><kwd>Homeoproteins</kwd><kwd>Parkinson disease</kwd><kwd>Engrailed</kwd><kwd>Mitochondria</kwd><kwd>Substantia nigra pars compacta</kwd><kwd>Retrograde degeneration</kwd></kwd-group></article-meta></front></pmc><affiliations><list></list><tree><noCountry><name sortKey="Blaudin De The, Francois Xavier" sort="Blaudin De The, Francois Xavier" uniqKey="Blaudin De The F" first="François-Xavier" last="Blaudin De Thé">François-Xavier Blaudin De Thé</name><name sortKey="Fuchs, Julia" sort="Fuchs, Julia" uniqKey="Fuchs J" first="Julia" last="Fuchs">Julia Fuchs</name><name sortKey="Joshi, Rajiv L" sort="Joshi, Rajiv L" uniqKey="Joshi R" first="Rajiv L." last="Joshi">Rajiv L. Joshi</name><name sortKey="Prochiantz, Alain" sort="Prochiantz, Alain" uniqKey="Prochiantz A" first="Alain" last="Prochiantz">Alain Prochiantz</name><name sortKey="Rekaik, Hocine" sort="Rekaik, Hocine" uniqKey="Rekaik H" first="Hocine" last="Rekaik">Hocine Rekaik</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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