Journal article
Synaptic abnormalities in a Drosophila model of Alzheimer’s disease
Disease models & mechanisms, v 7(3), pp 373-385
Mar 2014
PMID: 24487408
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
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.
Metrics
Details
- Title
- Synaptic abnormalities in a Drosophila model of Alzheimer’s disease
- Creators
- Siddhita D Mhatre - Department of Biology, Drexel University, Philadelphia, PA 19104, USAVivek Satyasi - Department of Biology, Drexel University, Philadelphia, PA 19104, USAMark Killen - Department of Biology, Drexel University, Philadelphia, PA 19104, USABrie E Paddock - Department of Biology, Arcadia University, Glenside, PA 19038, USARobert D Moir - Genetics and Aging Research Unit, MIND, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USAAleister J Saunders - Department of Biology, Drexel University, Philadelphia, PA 19104, USADaniel R Marenda - Department of Biology, Drexel University, Philadelphia, PA 19104, USA
- Publication Details
- Disease models & mechanisms, v 7(3), pp 373-385
- Publisher
- The Company of Biologists Limited
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biology
- Web of Science ID
- WOS:000337620300008
- Scopus ID
- 2-s2.0-84897147375
- Other Identifier
- 991014878077904721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Cell Biology
- Medicine, Research & Experimental
- Pathology