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Characterization of a Drosophila Alzheimer's disease model: pharmacological rescue of cognitive defects
Journal article   Open access

Characterization of a Drosophila Alzheimer's disease model: pharmacological rescue of cognitive defects

Ranjita Chakraborty, Vidya Vepuri, Siddhita D Mhatre, Brie E Paddock, Sean Miller, Sarah J Michelson, Radha Delvadia, Arkit Desai, Marianna Vinokur, David J Melicharek, …
PloS one, v 6(6), e20799
2011
DOI: https://doi.org/10.1371/journal.pone.0020799
PMID: 21673973
Featured in Collection :   UN Sustainable Development Goals @ Drexel
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https://doi.org/10.1371/journal.pone.0020799View
Published, Version of Record (VoR)CC BY V4.0,  Open

Abstract

Gene Expression Regulation, Enzymologic - drug effects Motor Activity - physiology Reflex - physiology Humans Motor Activity - drug effects Reflex - drug effects Male Brain - growth & development Brain - metabolism Protease Inhibitors - pharmacology Time Factors Amyloid beta-Protein Precursor - metabolism Cognition - physiology Behavior, Animal - drug effects Female Drug Evaluation, Preclinical Protease Inhibitors - therapeutic use Carbamates - pharmacology Disease Models, Animal Alzheimer Disease - physiopathology Dipeptides - therapeutic use Brain - physiopathology Dipeptides - pharmacology Alzheimer Disease - drug therapy Behavior, Animal - physiology Cognition - drug effects Brain - drug effects Amyloid Precursor Protein Secretases - metabolism Animals Alzheimer Disease - metabolism Amyloid Precursor Protein Secretases - antagonists & inhibitors Carbamates - therapeutic use Drosophila melanogaster Phenotype
Transgenic models of Alzheimer's disease (AD) have made significant contributions to our understanding of AD pathogenesis, and are useful tools in the development of potential therapeutics. The fruit fly, Drosophila melanogaster, provides a genetically tractable, powerful system to study the biochemical, genetic, environmental, and behavioral aspects of complex human diseases, including AD. In an effort to model AD, we over-expressed human APP and BACE genes in the Drosophila central nervous system. Biochemical, neuroanatomical, and behavioral analyses indicate that these flies exhibit aspects of clinical AD neuropathology and symptomology. These include the generation of Aβ(40) and Aβ(42), the presence of amyloid aggregates, dramatic neuroanatomical changes, defects in motor reflex behavior, and defects in memory. In addition, these flies exhibit external morphological abnormalities. Treatment with a γ-secretase inhibitor suppressed these phenotypes. Further, all of these phenotypes are present within the first few days of adult fly life. Taken together these data demonstrate that this transgenic AD model can serve as a powerful tool for the identification of AD therapeutic interventions.

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Collaboration types
Domestic collaboration
Web of Science research areas
Neurosciences
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