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

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 bi...

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Main Authors: Ranjita Chakraborty, Vidya Vepuri, Siddhita D Mhatre, Brie E Paddock, Sean Miller, Sarah J Michelson, Radha Delvadia, Arkit Desai, Marianna Vinokur, David J Melicharek, Suruchi Utreja, Preeti Khandelwal, Sara Ansaloni, Lee E Goldstein, Robert D Moir, Jeremy C Lee, Loni P Tabb, Aleister J Saunders, Daniel R Marenda
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2011-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3108982?pdf=render
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spelling doaj-9c5c36dfc5cc4bb28ba49db18bb2484d2020-11-25T01:46:28ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0166e2079910.1371/journal.pone.0020799Characterization of a Drosophila Alzheimer's disease model: pharmacological rescue of cognitive defects.Ranjita ChakrabortyVidya VepuriSiddhita D MhatreBrie E PaddockSean MillerSarah J MichelsonRadha DelvadiaArkit DesaiMarianna VinokurDavid J MelicharekSuruchi UtrejaPreeti KhandelwalSara AnsaloniLee E GoldsteinRobert D MoirJeremy C LeeLoni P TabbAleister J SaundersDaniel R MarendaTransgenic 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.http://europepmc.org/articles/PMC3108982?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Ranjita Chakraborty
Vidya Vepuri
Siddhita D Mhatre
Brie E Paddock
Sean Miller
Sarah J Michelson
Radha Delvadia
Arkit Desai
Marianna Vinokur
David J Melicharek
Suruchi Utreja
Preeti Khandelwal
Sara Ansaloni
Lee E Goldstein
Robert D Moir
Jeremy C Lee
Loni P Tabb
Aleister J Saunders
Daniel R Marenda
spellingShingle Ranjita Chakraborty
Vidya Vepuri
Siddhita D Mhatre
Brie E Paddock
Sean Miller
Sarah J Michelson
Radha Delvadia
Arkit Desai
Marianna Vinokur
David J Melicharek
Suruchi Utreja
Preeti Khandelwal
Sara Ansaloni
Lee E Goldstein
Robert D Moir
Jeremy C Lee
Loni P Tabb
Aleister J Saunders
Daniel R Marenda
Characterization of a Drosophila Alzheimer's disease model: pharmacological rescue of cognitive defects.
PLoS ONE
author_facet Ranjita Chakraborty
Vidya Vepuri
Siddhita D Mhatre
Brie E Paddock
Sean Miller
Sarah J Michelson
Radha Delvadia
Arkit Desai
Marianna Vinokur
David J Melicharek
Suruchi Utreja
Preeti Khandelwal
Sara Ansaloni
Lee E Goldstein
Robert D Moir
Jeremy C Lee
Loni P Tabb
Aleister J Saunders
Daniel R Marenda
author_sort Ranjita Chakraborty
title Characterization of a Drosophila Alzheimer's disease model: pharmacological rescue of cognitive defects.
title_short Characterization of a Drosophila Alzheimer's disease model: pharmacological rescue of cognitive defects.
title_full Characterization of a Drosophila Alzheimer's disease model: pharmacological rescue of cognitive defects.
title_fullStr Characterization of a Drosophila Alzheimer's disease model: pharmacological rescue of cognitive defects.
title_full_unstemmed Characterization of a Drosophila Alzheimer's disease model: pharmacological rescue of cognitive defects.
title_sort characterization of a drosophila alzheimer's disease model: pharmacological rescue of cognitive defects.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2011-01-01
description 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.
url http://europepmc.org/articles/PMC3108982?pdf=render
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