The Bcl-2 homologue Buffy rescues α-synuclein-induced Parkinson disease-like phenotypes in Drosophila
Identifieur interne : 000185 ( Main/Exploration ); précédent : 000184; suivant : 000186The Bcl-2 homologue Buffy rescues α-synuclein-induced Parkinson disease-like phenotypes in Drosophila
Auteurs : P. Githure M Ngale ; Brian E. StaveleySource :
- BMC Neuroscience [ 1471-2202 ] ; 2016.
Abstract
In contrast to the complexity found in mammals, only two
To alter the expression of
The inhibition of Buffy in DA neurons produces a novel model of PD in Drosophila. The directed expression of
Url:
DOI: 10.1186/s12868-016-0261-z
PubMed: 27192974
PubMed Central: 4872331
Affiliations:
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">The <italic>Bcl</italic>-<italic>2</italic> homologue <italic>Buffy</italic> rescues <italic>α</italic>-<italic>synuclein</italic>-induced Parkinson disease-like phenotypes in Drosophila</title><author><name sortKey="M Ngale, P Githure" sort="M Ngale, P Githure" uniqKey="M Ngale P" first="P. Githure" last="M Ngale">P. Githure M Ngale</name><affiliation><nlm:aff id="Aff1">Department of Biology, Memorial University of Newfoundland, St. John’s, NL A1B 3X9 Canada</nlm:aff><wicri:noCountry code="subfield">NL A1B 3X9 Canada</wicri:noCountry></affiliation></author><author><name sortKey="Staveley, Brian E" sort="Staveley, Brian E" uniqKey="Staveley B" first="Brian E." last="Staveley">Brian E. Staveley</name><affiliation><nlm:aff id="Aff1">Department of Biology, Memorial University of Newfoundland, St. John’s, NL A1B 3X9 Canada</nlm:aff><wicri:noCountry code="subfield">NL A1B 3X9 Canada</wicri:noCountry></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">27192974</idno><idno type="pmc">4872331</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872331</idno><idno type="RBID">PMC:4872331</idno><idno type="doi">10.1186/s12868-016-0261-z</idno><date when="2016">2016</date><idno type="wicri:Area/Pmc/Corpus">000241</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000241</idno><idno type="wicri:Area/Pmc/Curation">000241</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000241</idno><idno type="wicri:Area/Pmc/Checkpoint">000057</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000057</idno><idno type="wicri:source">PubMed</idno><idno type="wicri:Area/PubMed/Corpus">000230</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000230</idno><idno type="wicri:Area/PubMed/Curation">000230</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000230</idno><idno type="wicri:Area/PubMed/Checkpoint">000230</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000230</idno><idno type="wicri:Area/Ncbi/Merge">001F81</idno><idno type="wicri:Area/Ncbi/Curation">001F81</idno><idno type="wicri:Area/Ncbi/Checkpoint">001F81</idno><idno type="wicri:Area/Main/Merge">000185</idno><idno type="wicri:Area/Main/Curation">000185</idno><idno type="wicri:Area/Main/Exploration">000185</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">The <italic>Bcl</italic>-<italic>2</italic> homologue <italic>Buffy</italic> rescues <italic>α</italic>-<italic>synuclein</italic>-induced Parkinson disease-like phenotypes in Drosophila</title><author><name sortKey="M Ngale, P Githure" sort="M Ngale, P Githure" uniqKey="M Ngale P" first="P. Githure" last="M Ngale">P. Githure M Ngale</name><affiliation><nlm:aff id="Aff1">Department of Biology, Memorial University of Newfoundland, St. John’s, NL A1B 3X9 Canada</nlm:aff><wicri:noCountry code="subfield">NL A1B 3X9 Canada</wicri:noCountry></affiliation></author><author><name sortKey="Staveley, Brian E" sort="Staveley, Brian E" uniqKey="Staveley B" first="Brian E." last="Staveley">Brian E. Staveley</name><affiliation><nlm:aff id="Aff1">Department of Biology, Memorial University of Newfoundland, St. John’s, NL A1B 3X9 Canada</nlm:aff><wicri:noCountry code="subfield">NL A1B 3X9 Canada</wicri:noCountry></affiliation></author></analytic><series><title level="j">BMC Neuroscience</title><idno type="eISSN">1471-2202</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>In contrast to the complexity found in mammals, only two <italic>Bcl</italic>-<italic>2</italic> family genes have been found in <italic>Drosophila melanogaster</italic> including the pro-cell survival, human <italic>Bok</italic>-related orthologue, <italic>Buffy.</italic> The directed expression of <italic>α</italic>-<italic>synuclein</italic>, the first gene identified to contribute to inherited forms of Parkinson disease (PD), in the dopaminergic neurons (DA) of flies has provided a robust and well-studied Drosophila model of PD complete with the loss of neurons and accompanying motor defects. To more fully understand the biological basis of <italic>Bcl</italic>-<italic>2</italic> genes in PD, we altered the expression of <italic>Buffy</italic> in the dopamine producing neurons with and without the expression of <italic>α</italic>-<italic>synuclein,</italic> and in the developing neuron-rich eye.</p></sec><sec><title>Results</title><p>To alter the expression of <italic>Buffy</italic> in the dopaminergic neurons of Drosophila, the <italic>Ddc</italic>-<italic>Gal4</italic> transgene was used. The directed expression of <italic>Buffy</italic> in the dopamine producing neurons resulted in flies with increased climbing ability and enhanced survival, while the inhibition of <italic>Buffy</italic> in the dopaminergic neurons reduced climbing ability over time prematurely, similar to the phenotype observed in the <italic>α</italic>-<italic>synuclein</italic>-induced Drosophila model of PD. Subsequently, the expression of <italic>Buffy</italic> was altered in the <italic>α</italic>-<italic>synuclein</italic>-induced Drosophila model of PD. Analysis revealed that <italic>Buffy</italic> acted to rescue the associated loss of locomotor ability observed in the <italic>α</italic>-<italic>synuclein</italic>-induced model of PD, while Buffy RNA interference resulted in an enhanced <italic>α</italic>-<italic>synuclein</italic>-induced loss of climbing ability. In complementary experiments the overexpression of <italic>Buffy</italic> in the developing eye suppressed the mild rough eye phenotype that results from <italic>Gal4</italic> expression and from <italic>α</italic>-<italic>synuclein</italic> expression. When Buffy is inhibited the roughened eye phenotype is enhanced.</p></sec><sec><title>Conclusions</title><p>The inhibition of Buffy in DA neurons produces a novel model of PD in Drosophila. The directed expression of <italic>Buffy</italic> in DA neurons provide protection and counteracts the <italic>α</italic>-<italic>synuclein</italic>-induced Parkinson disease-like phenotypes. Taken all together this demonstrates a role for <italic>Buffy</italic>, a <italic>Bcl</italic>-<italic>2</italic> pro-cell survival gene, in neuroprotection.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Forno, Ls" uniqKey="Forno L">LS Forno</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Forno, Ls" uniqKey="Forno L">LS Forno</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Polymeropoulos, Mh" uniqKey="Polymeropoulos M">MH Polymeropoulos</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Leroy, E" uniqKey="Leroy E">E Leroy</name></author><author><name sortKey="Boyer, R" uniqKey="Boyer R">R Boyer</name></author><author><name sortKey="Auburger, G" uniqKey="Auburger G">G Auburger</name></author><author><name sortKey="Leube, B" uniqKey="Leube B">B Leube</name></author><author><name sortKey="Ulm, G" uniqKey="Ulm G">G 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sortKey="Daish, T" uniqKey="Daish T">T Daish</name></author><author><name sortKey="Colussi, P" uniqKey="Colussi P">P Colussi</name></author><author><name sortKey="Kumar, S" uniqKey="Kumar S">S Kumar</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wu, Jn" uniqKey="Wu J">JN Wu</name></author><author><name sortKey="Nguyen, N" uniqKey="Nguyen N">N Nguyen</name></author><author><name sortKey="Aghazarian, M" uniqKey="Aghazarian M">M Aghazarian</name></author><author><name sortKey="Tan, Y" uniqKey="Tan Y">Y Tan</name></author><author><name sortKey="Sevrioukov, Ea" uniqKey="Sevrioukov E">EA Sevrioukov</name></author><author><name sortKey="Mabuchi, M" uniqKey="Mabuchi M">M Mabuchi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Haywood, Af" uniqKey="Haywood A">AF Haywood</name></author><author><name sortKey="Staveley, Be" uniqKey="Staveley B">BE Staveley</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Haywood, Af" uniqKey="Haywood A">AF Haywood</name></author><author><name sortKey="Staveley, Be" uniqKey="Staveley B">BE Staveley</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Todd, Am" uniqKey="Todd A">AM Todd</name></author><author><name sortKey="Staveley, Be" uniqKey="Staveley B">BE Staveley</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Clavier, A" uniqKey="Clavier A">A Clavier</name></author><author><name sortKey="Baillet, A" uniqKey="Baillet A">A Baillet</name></author><author><name sortKey="Rincheval Arnold, A" uniqKey="Rincheval Arnold A">A Rincheval-Arnold</name></author><author><name sortKey="Coleno Costes, A" uniqKey="Coleno Costes A">A Coleno-Costes</name></author><author><name sortKey="Lasbleiz, C" uniqKey="Lasbleiz C">C Lasbleiz</name></author><author><name sortKey="Mignotte, B" uniqKey="Mignotte B">B 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Todd</name></author><author><name sortKey="Staveley, Be" uniqKey="Staveley B">BE Staveley</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Schneider, Ca" uniqKey="Schneider C">CA Schneider</name></author><author><name sortKey="Rasband, Ws" uniqKey="Rasband W">WS Rasband</name></author><author><name sortKey="Eliceiri, Kw" uniqKey="Eliceiri K">KW Eliceiri</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="M Ngale, Pg" uniqKey="M Ngale P">PG M’Angale</name></author><author><name sortKey="Staveley, Be" uniqKey="Staveley B">BE Staveley</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sievers, F" uniqKey="Sievers F">F Sievers</name></author><author><name sortKey="Wilm, A" uniqKey="Wilm A">A Wilm</name></author><author><name sortKey="Dineen, D" uniqKey="Dineen D">D Dineen</name></author><author><name sortKey="Gibson, Tj" uniqKey="Gibson T">TJ Gibson</name></author><author><name sortKey="Karplus, K" uniqKey="Karplus K">K Karplus</name></author><author><name sortKey="Li, W" uniqKey="Li W">W Li</name></author><author><name sortKey="Lopez, R" uniqKey="Lopez R">R Lopez</name></author><author><name sortKey="Mcwilliam, H" uniqKey="Mcwilliam H">H McWilliam</name></author><author><name sortKey="Remmert, M" uniqKey="Remmert M">M Remmert</name></author><author><name sortKey="Soding, J" uniqKey="Soding J">J Söding</name></author><author><name sortKey="Thompson, Jd" uniqKey="Thompson J">JD Thompson</name></author><author><name sortKey="Higgins, Dg" uniqKey="Higgins D">DG Higgins</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Goujon, M" uniqKey="Goujon M">M Goujon</name></author><author><name sortKey="Mcwilliam, H" uniqKey="Mcwilliam H">H McWilliam</name></author><author><name sortKey="Li, W" uniqKey="Li W">W Li</name></author><author><name sortKey="Valentin, F" uniqKey="Valentin F">F Valentin</name></author><author><name sortKey="Squizzato, S" uniqKey="Squizzato S">S Squizzato</name></author><author><name sortKey="Paern, J" uniqKey="Paern J">J Paern</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Marchler Bauer, A" uniqKey="Marchler Bauer A">A Marchler-Bauer</name></author><author><name sortKey="Derbyshire, Mk" uniqKey="Derbyshire M">MK Derbyshire</name></author><author><name sortKey="Gonzales, Nr" uniqKey="Gonzales N">NR Gonzales</name></author><author><name sortKey="Lu, S" uniqKey="Lu S">S Lu</name></author><author><name sortKey="Chitsaz, F" uniqKey="Chitsaz F">F Chitsaz</name></author><author><name sortKey="Geer, Ly" uniqKey="Geer L">LY Geer</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list></list><tree><noCountry><name sortKey="M Ngale, P Githure" sort="M Ngale, P Githure" uniqKey="M Ngale P" first="P. Githure" last="M Ngale">P. Githure M Ngale</name><name sortKey="Staveley, Brian E" sort="Staveley, Brian E" uniqKey="Staveley B" first="Brian E." last="Staveley">Brian E. Staveley</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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