The HtrA2 Drosophila model of Parkinson's disease is suppressed by the pro-survival Bcl-2 Buffy.
Identifieur interne : 000016 ( Main/Exploration ); précédent : 000015; suivant : 000017The HtrA2 Drosophila model of Parkinson's disease is suppressed by the pro-survival Bcl-2 Buffy.
Auteurs : P Githure M'Angale [Canada] ; Brian E. Staveley [Canada]Source :
- Genome [ 1480-3321 ] ; 2017.
English descriptors
- KwdEn :
- Aging (genetics), Amino Acid Sequence, Animals, Cell Survival (genetics), Conserved Sequence, Disease Models, Animal, Drosophila (genetics), Drosophila (metabolism), Drosophila Proteins (chemistry), Drosophila Proteins (genetics), Drosophila Proteins (metabolism), Gene Expression, Locomotion (genetics), Neurons (metabolism), PDZ Domains, Parkinson Disease (genetics), Parkinson Disease (metabolism), Parkinson Disease (physiopathology), Phenotype, Proto-Oncogene Proteins c-bcl-2 (genetics), Proto-Oncogene Proteins c-bcl-2 (metabolism), Serine Endopeptidases (chemistry), Serine Endopeptidases (genetics), Serine Endopeptidases (metabolism).
- MESH :
- chemical , chemistry : Drosophila Proteins, Serine Endopeptidases.
- genetics : Aging, Cell Survival, Drosophila, Drosophila Proteins, Locomotion, Parkinson Disease, Proto-Oncogene Proteins c-bcl-2, Serine Endopeptidases.
- metabolism : Drosophila, Drosophila Proteins, Neurons, Parkinson Disease, Proto-Oncogene Proteins c-bcl-2, Serine Endopeptidases.
- physiopathology : Parkinson Disease.
- Amino Acid Sequence, Animals, Conserved Sequence, Disease Models, Animal, Gene Expression, PDZ Domains, Phenotype.
Abstract
Mutations in High temperature requirement A2 (HtrA2), also designated PARK13, which lead to the loss of its protease activity, have been associated with Parkinson's disease (PD). HtrA2 is a mitochondrial protease that translocates to the cytosol upon the initiation of apoptosis where it participates in the abrogation of inhibitors of apoptosis (IAP) inhibition of caspases. Here, we demonstrate that the loss of the HtrA2 function in the dopaminergic neurons of Drosophila melanogaster results in PD-like phenotypes, and we attempt to restore the age-dependent loss in locomotor ability by co-expressing the sole pro-survival Bcl-2 homologue Buffy. The inhibition of HtrA2 in the dopaminergic neurons of Drosophila resulted in shortened lifespan and impaired climbing ability, and the overexpression of Buffy rescued the reduction in lifespan and the age-dependent loss of locomotor ability. In supportive experiments, the inhibition of HtrA2 in the Drosophila eye results in eye defects, marked by reduction in ommatidia number and increased disruption of the ommatidial array; phenotypes that are suppressed by the overexpression of Buffy.
DOI: 10.1139/gen-2016-0069
PubMed: 27848260
Affiliations:
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Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">The HtrA2 Drosophila model of Parkinson's disease is suppressed by the pro-survival Bcl-2 Buffy.</title><author><name sortKey="M Angale, P Githure" sort="M Angale, P Githure" uniqKey="M Angale P" first="P Githure" last="M'Angale">P Githure M'Angale</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biology, Memorial University of Newfoundland, St. John's, NL A1B 3X9, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Biology, Memorial University of Newfoundland, St. John's, NL A1B 3X9</wicri:regionArea><wicri:noRegion>NL A1B 3X9</wicri:noRegion></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 wicri:level="1"><nlm:affiliation>Department of Biology, Memorial University of Newfoundland, St. John's, NL A1B 3X9, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Biology, Memorial University of Newfoundland, St. John's, NL A1B 3X9</wicri:regionArea><wicri:noRegion>NL A1B 3X9</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2017">2017</date><idno type="RBID">pubmed:27848260</idno><idno type="pmid">27848260</idno><idno type="doi">10.1139/gen-2016-0069</idno><idno type="wicri:Area/PubMed/Corpus">000094</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000094</idno><idno type="wicri:Area/PubMed/Curation">000094</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000094</idno><idno type="wicri:Area/PubMed/Checkpoint">000094</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000094</idno><idno type="wicri:Area/Ncbi/Merge">002144</idno><idno type="wicri:Area/Ncbi/Curation">002144</idno><idno type="wicri:Area/Ncbi/Checkpoint">002144</idno><idno type="wicri:Area/Main/Merge">000016</idno><idno type="wicri:Area/Main/Curation">000016</idno><idno type="wicri:Area/Main/Exploration">000016</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">The HtrA2 Drosophila model of Parkinson's disease is suppressed by the pro-survival Bcl-2 Buffy.</title><author><name sortKey="M Angale, P Githure" sort="M Angale, P Githure" uniqKey="M Angale P" first="P Githure" last="M'Angale">P Githure M'Angale</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biology, Memorial University of Newfoundland, St. John's, NL A1B 3X9, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Biology, Memorial University of Newfoundland, St. John's, NL A1B 3X9</wicri:regionArea><wicri:noRegion>NL A1B 3X9</wicri:noRegion></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 wicri:level="1"><nlm:affiliation>Department of Biology, Memorial University of Newfoundland, St. John's, NL A1B 3X9, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Biology, Memorial University of Newfoundland, St. John's, NL A1B 3X9</wicri:regionArea><wicri:noRegion>NL A1B 3X9</wicri:noRegion></affiliation></author></analytic><series><title level="j">Genome</title><idno type="eISSN">1480-3321</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Aging (genetics)</term><term>Amino Acid Sequence</term><term>Animals</term><term>Cell Survival (genetics)</term><term>Conserved Sequence</term><term>Disease Models, Animal</term><term>Drosophila (genetics)</term><term>Drosophila (metabolism)</term><term>Drosophila Proteins (chemistry)</term><term>Drosophila Proteins (genetics)</term><term>Drosophila Proteins (metabolism)</term><term>Gene Expression</term><term>Locomotion (genetics)</term><term>Neurons (metabolism)</term><term>PDZ Domains</term><term>Parkinson Disease (genetics)</term><term>Parkinson Disease (metabolism)</term><term>Parkinson Disease (physiopathology)</term><term>Phenotype</term><term>Proto-Oncogene Proteins c-bcl-2 (genetics)</term><term>Proto-Oncogene Proteins c-bcl-2 (metabolism)</term><term>Serine Endopeptidases (chemistry)</term><term>Serine Endopeptidases (genetics)</term><term>Serine Endopeptidases (metabolism)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Drosophila Proteins</term><term>Serine Endopeptidases</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Aging</term><term>Cell Survival</term><term>Drosophila</term><term>Drosophila Proteins</term><term>Locomotion</term><term>Parkinson Disease</term><term>Proto-Oncogene Proteins c-bcl-2</term><term>Serine Endopeptidases</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Drosophila</term><term>Drosophila Proteins</term><term>Neurons</term><term>Parkinson Disease</term><term>Proto-Oncogene Proteins c-bcl-2</term><term>Serine Endopeptidases</term></keywords><keywords scheme="MESH" qualifier="physiopathology" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Amino Acid Sequence</term><term>Animals</term><term>Conserved Sequence</term><term>Disease Models, Animal</term><term>Gene Expression</term><term>PDZ Domains</term><term>Phenotype</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Mutations in High temperature requirement A2 (HtrA2), also designated PARK13, which lead to the loss of its protease activity, have been associated with Parkinson's disease (PD). HtrA2 is a mitochondrial protease that translocates to the cytosol upon the initiation of apoptosis where it participates in the abrogation of inhibitors of apoptosis (IAP) inhibition of caspases. Here, we demonstrate that the loss of the HtrA2 function in the dopaminergic neurons of Drosophila melanogaster results in PD-like phenotypes, and we attempt to restore the age-dependent loss in locomotor ability by co-expressing the sole pro-survival Bcl-2 homologue Buffy. The inhibition of HtrA2 in the dopaminergic neurons of Drosophila resulted in shortened lifespan and impaired climbing ability, and the overexpression of Buffy rescued the reduction in lifespan and the age-dependent loss of locomotor ability. In supportive experiments, the inhibition of HtrA2 in the Drosophila eye results in eye defects, marked by reduction in ommatidia number and increased disruption of the ommatidial array; phenotypes that are suppressed by the overexpression of Buffy.</div></front></TEI><affiliations><list><country><li>Canada</li></country></list><tree><country name="Canada"><noRegion><name sortKey="M Angale, P Githure" sort="M Angale, P Githure" uniqKey="M Angale P" first="P Githure" last="M'Angale">P Githure M'Angale</name></noRegion><name sortKey="Staveley, Brian E" sort="Staveley, Brian E" uniqKey="Staveley B" first="Brian E" last="Staveley">Brian E. Staveley</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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