spargel, the PGC-1α homologue, in models of Parkinson disease in Drosophila melanogaster
Identifieur interne : 000369 ( Pmc/Checkpoint ); précédent : 000368; suivant : 000370spargel, the PGC-1α homologue, in models of Parkinson disease in Drosophila melanogaster
Auteurs : Eric M. Merzetti ; Brian E. StaveleySource :
- BMC Neuroscience [ 1471-2202 ] ; 2015.
Abstract
Parkinson disease (PD) is a progressive neurodegenerative disorder presenting with symptoms of resting tremor, bradykinesia, rigidity, postural instability and additional severe cognitive impairment over time. These symptoms arise from a decrease of available dopamine in the striatum of the brain resulting from the breakdown and death of dopaminergic (DA) neurons. A process implicated in the destruction of these neurons is mitochondrial breakdown and impairment. Upkeep and repair of mitochondria involves a number of complex and key components including
Directed expression of
The reduced lifespan and climbing ability associated with a tissue specific expression of
Url:
DOI: 10.1186/s12868-015-0210-2
PubMed: 26502946
PubMed Central: 4623274
Affiliations:
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PMC:4623274Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en"><italic>spargel</italic>
, the <italic>PGC</italic>
-<italic>1α</italic>
homologue, in models of Parkinson disease in <italic>Drosophila melanogaster</italic>
</title>
<author><name sortKey="Merzetti, Eric M" sort="Merzetti, Eric M" uniqKey="Merzetti E" first="Eric M." last="Merzetti">Eric M. Merzetti</name>
<affiliation><nlm:aff id="Aff1">Department of Biology, Memorial University of Newfoundland, 232 Elizabeth Avenue, 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, 232 Elizabeth Avenue, St. John’s, NL A1B 3X9 Canada</nlm:aff>
<wicri:noCountry code="subfield">NL A1B 3X9 Canada</wicri:noCountry>
</affiliation>
</author>
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<idno type="doi">10.1186/s12868-015-0210-2</idno>
<date when="2015">2015</date>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main"><italic>spargel</italic>
, the <italic>PGC</italic>
-<italic>1α</italic>
homologue, in models of Parkinson disease in <italic>Drosophila melanogaster</italic>
</title>
<author><name sortKey="Merzetti, Eric M" sort="Merzetti, Eric M" uniqKey="Merzetti E" first="Eric M." last="Merzetti">Eric M. Merzetti</name>
<affiliation><nlm:aff id="Aff1">Department of Biology, Memorial University of Newfoundland, 232 Elizabeth Avenue, 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, 232 Elizabeth Avenue, 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="2015">2015</date>
</imprint>
</series>
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<front><div type="abstract" xml:lang="en"><sec><title>Background</title>
<p>Parkinson disease (PD) is a progressive neurodegenerative disorder presenting with symptoms of resting tremor, bradykinesia, rigidity, postural instability and additional severe cognitive impairment over time. These symptoms arise from a decrease of available dopamine in the striatum of the brain resulting from the breakdown and death of dopaminergic (DA) neurons. A process implicated in the destruction of these neurons is mitochondrial breakdown and impairment. Upkeep and repair of mitochondria involves a number of complex and key components including <italic>Pink1</italic>
, <italic>Parkin</italic>
, and the PGC family of genes. <italic>PGC</italic>
-<italic>1α</italic>
has been characterized as a regulator of mitochondria biogenesis, insulin receptor signalling and energy metabolism, mutation of this gene has been linked to early onset forms of PD. The mammalian PGC family consists of three partially redundant genes making the study of full or partial loss of function difficult. The sole <italic>Drosophila melanogaster</italic>
homologue of this gene family, <italic>spargel</italic>
(<italic>srl</italic>
), has been shown to function in similar pathways of mitochondrial upkeep and biogenesis.</p>
</sec>
<sec><title>Results</title>
<p>Directed expression of <italic>srl</italic>
-<italic>RNAi</italic>
in the <italic>D. melanogaster</italic>
eye causes abnormal ommatidia and bristle formation while eye specific expression of <italic>srl</italic>
-<italic>EY</italic>
does not produce the minor rough eye phenotype associated with high temperature <italic>GMR</italic>
-<italic>Gal4</italic>
expression. <italic>Ddc</italic>
-<italic>Gal4</italic>
mediated tissue specific expression of <italic>srl</italic>
transgene constructs in <italic>D. melanogaster</italic>
DA neurons causes altered lifespan and climbing ability. Expression of a <italic>srl</italic>
-<italic>RNAi</italic>
causes an increase in mean lifespan but a decrease in overall loco-motor ability while induced expression of <italic>srl</italic>
-<italic>EY</italic>
causes a severe decrease in mean lifespan and a decrease in loco-motor ability.</p>
</sec>
<sec><title>Conclusions</title>
<p>The reduced lifespan and climbing ability associated with a tissue specific expression of <italic>srl</italic>
in DA neurons provides a new model of PD in <italic>D. melanogaster</italic>
which may be used to identify novel therapeutic approaches to human disease treatment and prevention.</p>
</sec>
</div>
</front>
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</author>
</analytic>
</biblStruct>
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</author>
<author><name sortKey="Eliceiri, Kw" uniqKey="Eliceiri K">KW Eliceiri</name>
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</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>
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</author>
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</author>
<author><name sortKey="Brown, Np" uniqKey="Brown N">NP Brown</name>
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</div1>
</back>
</TEI>
<pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">BMC Neurosci</journal-id>
<journal-id journal-id-type="iso-abbrev">BMC Neurosci</journal-id>
<journal-title-group><journal-title>BMC Neuroscience</journal-title>
</journal-title-group>
<issn pub-type="epub">1471-2202</issn>
<publisher><publisher-name>BioMed Central</publisher-name>
<publisher-loc>London</publisher-loc>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">26502946</article-id>
<article-id pub-id-type="pmc">4623274</article-id>
<article-id pub-id-type="publisher-id">210</article-id>
<article-id pub-id-type="doi">10.1186/s12868-015-0210-2</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject>
</subj-group>
</article-categories>
<title-group><article-title><italic>spargel</italic>
, the <italic>PGC</italic>
-<italic>1α</italic>
homologue, in models of Parkinson disease in <italic>Drosophila melanogaster</italic>
</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Merzetti</surname>
<given-names>Eric M.</given-names>
</name>
<address><email>emvm45@mun.ca</email>
</address>
<xref ref-type="aff" rid="Aff1"></xref>
</contrib>
<contrib contrib-type="author" corresp="yes"><name><surname>Staveley</surname>
<given-names>Brian E.</given-names>
</name>
<address><phone>1-709-864-4317</phone>
<email>bestave@mun.ca</email>
</address>
<xref ref-type="aff" rid="Aff1"></xref>
</contrib>
<aff id="Aff1">Department of Biology, Memorial University of Newfoundland, 232 Elizabeth Avenue, St. John’s, NL A1B 3X9 Canada</aff>
</contrib-group>
<pub-date pub-type="epub"><day>26</day>
<month>10</month>
<year>2015</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>26</day>
<month>10</month>
<year>2015</year>
</pub-date>
<pub-date pub-type="collection"><year>2015</year>
</pub-date>
<volume>16</volume>
<elocation-id>70</elocation-id>
<history><date date-type="received"><day>29</day>
<month>5</month>
<year>2015</year>
</date>
<date date-type="accepted"><day>12</day>
<month>10</month>
<year>2015</year>
</date>
</history>
<permissions><copyright-statement>© Merzetti and Staveley. 2015</copyright-statement>
<license license-type="OpenAccess"><license-p><bold>Open Access</bold>
This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>
), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/publicdomain/zero/1.0/">http://creativecommons.org/publicdomain/zero/1.0/</ext-link>
) applies to the data made available in this article, unless otherwise stated.</license-p>
</license>
</permissions>
<abstract id="Abs1"><sec><title>Background</title>
<p>Parkinson disease (PD) is a progressive neurodegenerative disorder presenting with symptoms of resting tremor, bradykinesia, rigidity, postural instability and additional severe cognitive impairment over time. These symptoms arise from a decrease of available dopamine in the striatum of the brain resulting from the breakdown and death of dopaminergic (DA) neurons. A process implicated in the destruction of these neurons is mitochondrial breakdown and impairment. Upkeep and repair of mitochondria involves a number of complex and key components including <italic>Pink1</italic>
, <italic>Parkin</italic>
, and the PGC family of genes. <italic>PGC</italic>
-<italic>1α</italic>
has been characterized as a regulator of mitochondria biogenesis, insulin receptor signalling and energy metabolism, mutation of this gene has been linked to early onset forms of PD. The mammalian PGC family consists of three partially redundant genes making the study of full or partial loss of function difficult. The sole <italic>Drosophila melanogaster</italic>
homologue of this gene family, <italic>spargel</italic>
(<italic>srl</italic>
), has been shown to function in similar pathways of mitochondrial upkeep and biogenesis.</p>
</sec>
<sec><title>Results</title>
<p>Directed expression of <italic>srl</italic>
-<italic>RNAi</italic>
in the <italic>D. melanogaster</italic>
eye causes abnormal ommatidia and bristle formation while eye specific expression of <italic>srl</italic>
-<italic>EY</italic>
does not produce the minor rough eye phenotype associated with high temperature <italic>GMR</italic>
-<italic>Gal4</italic>
expression. <italic>Ddc</italic>
-<italic>Gal4</italic>
mediated tissue specific expression of <italic>srl</italic>
transgene constructs in <italic>D. melanogaster</italic>
DA neurons causes altered lifespan and climbing ability. Expression of a <italic>srl</italic>
-<italic>RNAi</italic>
causes an increase in mean lifespan but a decrease in overall loco-motor ability while induced expression of <italic>srl</italic>
-<italic>EY</italic>
causes a severe decrease in mean lifespan and a decrease in loco-motor ability.</p>
</sec>
<sec><title>Conclusions</title>
<p>The reduced lifespan and climbing ability associated with a tissue specific expression of <italic>srl</italic>
in DA neurons provides a new model of PD in <italic>D. melanogaster</italic>
which may be used to identify novel therapeutic approaches to human disease treatment and prevention.</p>
</sec>
</abstract>
<kwd-group xml:lang="en"><title>Keywords</title>
<kwd><italic>spargel</italic>
</kwd>
<kwd><italic>PGC</italic>
-<italic>1α</italic>
</kwd>
<kwd>Neurodegeneration</kwd>
<kwd>Parkinson disease</kwd>
<kwd><italic>Drosophila melanogaster</italic>
</kwd>
</kwd-group>
<custom-meta-group><custom-meta><meta-name>issue-copyright-statement</meta-name>
<meta-value>© The Author(s) 2015</meta-value>
</custom-meta>
</custom-meta-group>
</article-meta>
</front>
</pmc>
<affiliations><list></list>
<tree><noCountry><name sortKey="Merzetti, Eric M" sort="Merzetti, Eric M" uniqKey="Merzetti E" first="Eric M." last="Merzetti">Eric M. Merzetti</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>
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