Synaptic abnormalities in a Drosophila model of Alzheimer’s disease
Alzheimer’s disease (AD) is an age-related neurodegenerative disease characterized by memory loss and decreased synaptic function. Advances in transgenic animal models of AD have facilitated our understanding of this disorder, and have aided in the development, speed and efficiency of testing potent...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
The Company of Biologists
2014-03-01
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| Series: | Disease Models & Mechanisms |
| Subjects: | |
| Online Access: | http://dmm.biologists.org/content/7/3/373 |
| _version_ | 1828470128503685120 |
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| author | Siddhita D. Mhatre Vivek Satyasi Mark Killen Brie E. Paddock Robert D. Moir Aleister J. Saunders Daniel R. Marenda |
| author_facet | Siddhita D. Mhatre Vivek Satyasi Mark Killen Brie E. Paddock Robert D. Moir Aleister J. Saunders Daniel R. Marenda |
| author_sort | Siddhita D. Mhatre |
| collection | DOAJ |
| description | Alzheimer’s disease (AD) is an age-related neurodegenerative disease characterized by memory loss and decreased synaptic function. Advances in transgenic animal models of AD have facilitated our understanding of this disorder, and have aided in the development, speed and efficiency of testing potential therapeutics. Recently, we have described the characterization of a novel model of AD in the fruit fly, Drosophila melanogaster, where we expressed the human AD-associated proteins APP and BACE in the central nervous system of the fly. Here we describe synaptic defects in the larval neuromuscular junction (NMJ) in this model. Our results indicate that expression of human APP and BACE at the larval NMJ leads to defective larval locomotion behavior, decreased presynaptic connections, altered mitochondrial localization in presynaptic motor neurons and decreased postsynaptic protein levels. Treating larvae expressing APP and BACE with the γ-secretase inhibitor L-685,458 suppresses the behavioral defects as well as the pre- and postsynaptic defects. We suggest that this model will be useful to assess and model the synaptic dysfunction normally associated with AD, and will also serve as a powerful in vivo tool for rapid testing of potential therapeutics for AD. |
| first_indexed | 2024-12-11T04:48:12Z |
| format | Article |
| id | doaj.art-c4ad97fcfa7e4458a465841d6ca134e5 |
| institution | Directory Open Access Journal |
| issn | 1754-8403 1754-8411 |
| language | English |
| last_indexed | 2024-12-11T04:48:12Z |
| publishDate | 2014-03-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Disease Models & Mechanisms |
| spelling | doaj.art-c4ad97fcfa7e4458a465841d6ca134e52022-12-22T01:20:27ZengThe Company of BiologistsDisease Models & Mechanisms1754-84031754-84112014-03-017337338510.1242/dmm.012104012104Synaptic abnormalities in a Drosophila model of Alzheimer’s diseaseSiddhita D. MhatreVivek SatyasiMark KillenBrie E. PaddockRobert D. MoirAleister J. SaundersDaniel R. MarendaAlzheimer’s disease (AD) is an age-related neurodegenerative disease characterized by memory loss and decreased synaptic function. Advances in transgenic animal models of AD have facilitated our understanding of this disorder, and have aided in the development, speed and efficiency of testing potential therapeutics. Recently, we have described the characterization of a novel model of AD in the fruit fly, Drosophila melanogaster, where we expressed the human AD-associated proteins APP and BACE in the central nervous system of the fly. Here we describe synaptic defects in the larval neuromuscular junction (NMJ) in this model. Our results indicate that expression of human APP and BACE at the larval NMJ leads to defective larval locomotion behavior, decreased presynaptic connections, altered mitochondrial localization in presynaptic motor neurons and decreased postsynaptic protein levels. Treating larvae expressing APP and BACE with the γ-secretase inhibitor L-685,458 suppresses the behavioral defects as well as the pre- and postsynaptic defects. We suggest that this model will be useful to assess and model the synaptic dysfunction normally associated with AD, and will also serve as a powerful in vivo tool for rapid testing of potential therapeutics for AD.http://dmm.biologists.org/content/7/3/373APPAlzheimer’s diseaseDrosophilaBACESynapseNMJ |
| spellingShingle | Siddhita D. Mhatre Vivek Satyasi Mark Killen Brie E. Paddock Robert D. Moir Aleister J. Saunders Daniel R. Marenda Synaptic abnormalities in a Drosophila model of Alzheimer’s disease Disease Models & Mechanisms APP Alzheimer’s disease Drosophila BACE Synapse NMJ |
| title | Synaptic abnormalities in a Drosophila model of Alzheimer’s disease |
| title_full | Synaptic abnormalities in a Drosophila model of Alzheimer’s disease |
| title_fullStr | Synaptic abnormalities in a Drosophila model of Alzheimer’s disease |
| title_full_unstemmed | Synaptic abnormalities in a Drosophila model of Alzheimer’s disease |
| title_short | Synaptic abnormalities in a Drosophila model of Alzheimer’s disease |
| title_sort | synaptic abnormalities in a drosophila model of alzheimer s disease |
| topic | APP Alzheimer’s disease Drosophila BACE Synapse NMJ |
| url | http://dmm.biologists.org/content/7/3/373 |
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