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...
Main Authors: | , , , , , , , , , , , , , , , , , , |
---|---|
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 |
id |
doaj-9c5c36dfc5cc4bb28ba49db18bb2484d |
---|---|
record_format |
Article |
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 |
work_keys_str_mv |
AT ranjitachakraborty characterizationofadrosophilaalzheimersdiseasemodelpharmacologicalrescueofcognitivedefects AT vidyavepuri characterizationofadrosophilaalzheimersdiseasemodelpharmacologicalrescueofcognitivedefects AT siddhitadmhatre characterizationofadrosophilaalzheimersdiseasemodelpharmacologicalrescueofcognitivedefects AT brieepaddock characterizationofadrosophilaalzheimersdiseasemodelpharmacologicalrescueofcognitivedefects AT seanmiller characterizationofadrosophilaalzheimersdiseasemodelpharmacologicalrescueofcognitivedefects AT sarahjmichelson characterizationofadrosophilaalzheimersdiseasemodelpharmacologicalrescueofcognitivedefects AT radhadelvadia characterizationofadrosophilaalzheimersdiseasemodelpharmacologicalrescueofcognitivedefects AT arkitdesai characterizationofadrosophilaalzheimersdiseasemodelpharmacologicalrescueofcognitivedefects AT mariannavinokur characterizationofadrosophilaalzheimersdiseasemodelpharmacologicalrescueofcognitivedefects AT davidjmelicharek characterizationofadrosophilaalzheimersdiseasemodelpharmacologicalrescueofcognitivedefects AT suruchiutreja characterizationofadrosophilaalzheimersdiseasemodelpharmacologicalrescueofcognitivedefects AT preetikhandelwal characterizationofadrosophilaalzheimersdiseasemodelpharmacologicalrescueofcognitivedefects AT saraansaloni characterizationofadrosophilaalzheimersdiseasemodelpharmacologicalrescueofcognitivedefects AT leeegoldstein characterizationofadrosophilaalzheimersdiseasemodelpharmacologicalrescueofcognitivedefects AT robertdmoir characterizationofadrosophilaalzheimersdiseasemodelpharmacologicalrescueofcognitivedefects AT jeremyclee characterizationofadrosophilaalzheimersdiseasemodelpharmacologicalrescueofcognitivedefects AT loniptabb characterizationofadrosophilaalzheimersdiseasemodelpharmacologicalrescueofcognitivedefects AT aleisterjsaunders characterizationofadrosophilaalzheimersdiseasemodelpharmacologicalrescueofcognitivedefects AT danielrmarenda characterizationofadrosophilaalzheimersdiseasemodelpharmacologicalrescueofcognitivedefects |
_version_ |
1725019400414691328 |