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pdfcrowd.com Date: Tuesday, June 21, 2016 Session Title: Parkinson's disease: Genetics Session Time: 12:30pm-2:00pm Location: Exhibit Hall located in Hall B, Level 2 Reduced lifespan and climbing ability observed in the overexpressing human α-synuclein without heat shock protein CNB115 in Parkinson’s disease drosophila line M.S. Islam, H.J. Kim, S.S. Hong (Jeonju, Korea) Meeting: 20th International Congress Abstract Number: 635 Keywords: Alpha-synuclein, Dopamine, Heat shock proteins(HSP), Parkinsonism Session Information Objective: To investigate the neurotoxic role of overexpressing α-synuclein without Heat Shock Protein CNB115 (HSP115) in Parkinson’s disease Drosophila line. Background: Parkinson’s disease (PD) is a common human neurodegenerative movement disorder and is characterized by a progressive loss of dopaminergic neurons and abnormal accumulation of α-synuclein (α-syn) into aggregates called Lewy bodies. On the other hand, HSP115 is a fly homologue of the mammalian serine protease, a mitochondrial protein that has 50% amino acid sequence identity, domain structure similar to human serine protease that is high homology to a bacterial survival factor, HtrA which protects bacterial cells from stress-induced toxicity due to misfolded proteins. Methods: We Developed a Drosophila line expressing α-Syn without HSP115 by crossing α-Syn flies with knockout- HSP115 flies. Then α-Syn gene and knockout- HSP115 gene were identified after crossing with ELAV-GAL4 by polymerase chain reaction (PCR). We directed the pan neuronal and eye specific expression of α-syn without HSP115 by using ELAV-GAL4 and GMR-GAL4 driver line respectively. Results: Abnormal accumulation of α-syn, reduced lifespan, locomotors dysfunction, dopaminergic neuronal loss and damage eyes were resulted in 30 days old in the developed α-syn without HSP115 Drosophila line that indicates a toxic dominant mechanism of α-syn for the etiopathogenesis of PD. Conclusions: Our developed Drosophila line demonstrated the overexpression of intraneuronal accumulated α-syn protein without HSP115, suggesting the detrimental effects of α-syn without HSP115 in a Drosophila line of PD. References: 1. Amy M. Todd and Brian E. Staveley: Pink1 suppresses a- synuclein-induced phenotypes in a Drosophila model of Parkinson’s disease; Genome 51: 1040–1046 (2008). 2. Challa M, Malladi S, Pellock BJ, Dresnek D, Varadarajan S, Yin YW, White K, Bratton SB. Drosophila Omi, a mitochondrial-localized IAP antagonist and proapoptotic serine protease. EMBO J 2007; 26:3144-3156. To cite this abstract in AMA style: M.S. Islam, H.J. Kim, S.S. Hong. Reduced lifespan and climbing ability observed in the overexpressing

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Date: Tuesday, June 21, 2016

Session Title: Parkinson's disease: Genetics

Session Time: 12:30pm-2:00pm

Location: Exhibit Hall located in Hall B, Level 2

Reduced lifespan and climbing ability observed in theoverexpressing human α-synuclein without heatshock protein CNB115 in Parkinson’s diseasedrosophila line

M.S. Islam, H.J. Kim, S.S. Hong (Jeonju, Korea)

Meeting: 20th International Congress

Abstract Number: 635

Keywords: Alpha-synuclein, Dopamine, Heat shock proteins(HSP), Parkinsonism

Session Information

Objective: To investigate the neurotoxic role of overexpressing α-synuclein without Heat Shock ProteinCNB115 (HSP115) in Parkinson’s disease Drosophila line.

Background: Parkinson’s disease (PD) is a common human neurodegenerative movement disorder and ischaracterized by a progressive loss of dopaminergic neurons and abnormal accumulation of α-synuclein(α-syn) into aggregates called Lewy bodies. On the other hand, HSP115 is a fly homologue of themammalian serine protease, a mitochondrial protein that has 50% amino acid sequence identity, domainstructure similar to human serine protease that is high homology to a bacterial survival factor, HtrA whichprotects bacterial cells from stress-induced toxicity due to misfolded proteins.

Methods: We Developed a Drosophila line expressing α-Syn without HSP115 by crossing α-Syn flies withknockout- HSP115 flies. Then α-Syn gene and knockout- HSP115 gene were identified after crossing withELAV-GAL4 by polymerase chain reaction (PCR). We directed the pan neuronal and eye specific expressionof α-syn without HSP115 by using ELAV-GAL4 and GMR-GAL4 driver line respectively.

Results: Abnormal accumulation of α-syn, reduced lifespan, locomotors dysfunction, dopaminergicneuronal loss and damage eyes were resulted in 30 days old in the developed α-syn without HSP115Drosophila line that indicates a toxic dominant mechanism of α-syn for the etiopathogenesis of PD.

Conclusions: Our developed Drosophila line demonstrated the overexpression of intraneuronalaccumulated α-syn protein without HSP115, suggesting the detrimental effects of α-syn without HSP115in a Drosophila line of PD. References: 1. Amy M. Todd and Brian E. Staveley: Pink1 suppresses a-synuclein-induced phenotypes in a Drosophila model of Parkinson’s disease; Genome 51: 1040–1046(2008). 2. Challa M, Malladi S, Pellock BJ, Dresnek D, Varadarajan S, Yin YW, White K, Bratton SB.Drosophila Omi, a mitochondrial-localized IAP antagonist and proapoptotic serine protease. EMBO J2007; 26:3144-3156.

To cite this abstract in AMA style:

M.S. Islam, H.J. Kim, S.S. Hong. Reduced lifespan and climbing ability observed in the overexpressing

Page 2: Reduced_lifespan_and_climbing_ability_ob

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human α-synuclein without heat shock protein CNB115 in Parkinson’s disease drosophila line[abstract]. Mov Disord. 2016; 31 (suppl 2). http://www.mdsabstracts.org/abstract/reduced-lifespan-and-climbing-ability-observed-in-the-overexpressing-human-synuclein-without-heat-shock-protein-cnb115-in-parkinsons-disease-drosophila-line/. Accessed October 12, 2016.

MDS Abstracts - http://www.mdsabstracts.org/abstract/reduced-lifespan-and-climbing-ability-observed-in-the-overexpressing-human-synuclein-without-heat-shock-protein-cnb115-in-parkinsons-disease-drosophila-line/