A model for studying Alzheimer's Abeta42-induced toxicity in Drosophila melanogaster

Molecular and Cellular Neurosciences
Alyce FinelliMary Konsolaki

Abstract

Alzheimer's disease is a neurological disorder resulting in the degeneration and death of brain neurons controlling memory, cognition and behavior. Although overproduction of Abeta peptides is widely considered a causative event in the disease, the mechanisms by which Abeta peptides cause neurodegeneration and the processes of Abeta clearance and degradation remain unclear. To address these issues, we have expressed the Abeta peptides in Drosophila melanogaster. We show that overexpression of Abeta42 peptides in the nervous system results in phenotypes associated with neuronal degeneration in a dose- and age-dependent manner. We further show that a mutation in a Drosophila neprilysin gene suppresses the Abeta42 phenotypes by lowering the levels of the Abeta42 peptide, supporting the role of neprilysin in the catabolism of Abeta peptides in vivo. We propose that our Drosophila model is suitable for the study and elucidation of Abeta metabolism and toxicity at the genetic level.

References

Apr 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·D R RosenK White
Oct 22, 1982·Science·G M Rubin, A C Spradling
Sep 26, 1995·Proceedings of the National Academy of Sciences of the United States of America·C D Link
Jan 1, 1995·Methods in Enzymology·C Li, L B Hersh
Dec 6, 1994·Proceedings of the National Academy of Sciences of the United States of America·A Lorenzo, B A Yankner
Oct 29, 1996·Proceedings of the National Academy of Sciences of the United States of America·P Rørth
Mar 3, 1997·Neuroreport·G L BoulianneP St George-Hyslop
May 13, 1997·Proceedings of the National Academy of Sciences of the United States of America·B A HayG M Rubin
Feb 1, 1997·Chemistry & Biology·J D HarperP T Lansbury
Apr 18, 1998·Amyloid : the International Journal of Experimental and Clinical Investigation : the Official Journal of the International Society of Amyloidosis·A C McKeeM F Beal
Nov 13, 1998·Proceedings of the National Academy of Sciences of the United States of America·A FossgreenR Paro
Mar 10, 2000·Science·P Kazemi-Esfarjani, S Benzer
Mar 29, 2000·JAMA : the Journal of the American Medical Association·J NäslundJ D Buxbaum
Apr 4, 2000·Nature·M B Feany, W W Bender
Feb 24, 2001·Annals of the New York Academy of Sciences·J Poirier
Feb 27, 2001·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·A J TurnerD Coates
Mar 7, 2001·Frontiers in Bioscience : a Journal and Virtual Library·M Chen, H L Fernandez
May 26, 2001·Science·N IwataT C Saido

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Citations

Nov 14, 2008·European Biophysics Journal : EBJ·N SureshbabuR Jayakumar
Dec 8, 2009·Brain Structure & Function·Kanae Iijima-Ando, Koichi Iijima
Apr 18, 2009·Apoptosis : an International Journal on Programmed Cell Death·Bingwei Lu
Sep 1, 2005·Age·Gordon J LithgowJames N Sampayo
Jul 30, 2011·Journal of Biosciences·Weihuan Cao, Mary Konsolaki
Oct 12, 2012·Neuroscience Bulletin·Liqun FangYulan Zhu
Mar 8, 2005·Drug Discovery Today·Travis DunckleyDietrich A Stephan
Nov 3, 2004·Nature Reviews. Drug Discovery·Richard Kramer, Dalia Cohen
Oct 4, 2011·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Janet R KumitaAnn-Christin Brorsson
Apr 7, 2005·Genes, Brain, and Behavior·C D Link
Mar 19, 2009·Pharmacological Reviews·Steven D BuckinghamDavid B Sattelle
Mar 19, 2011·Pharmacological Reviews·Udai Bhan Pandey, Charles D Nichols
Feb 22, 2012·Biochemistry. Biokhimii︠a︡·V L Katanaev, M V Kryuchkov
Oct 10, 2008·Annual Review of Pathology·Bingwei Lu, Hannes Vogel
Aug 26, 2011·Developmental Neuroscience·Chunhong LiuY Eugene Yu
Nov 26, 2013·Molecular Neurodegeneration·Katja PrüßingJörg B Schulz
Aug 14, 2012·Disease Models & Mechanisms·Fabien D'AngeloChristelle Marchal
Nov 2, 2007·PLoS Biology·Leila M LuheshiDamian C Crowther
Jul 19, 2012·PloS One·Iain RogersLinda Partridge
Apr 23, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Kien TrinhLeo Pallanck
Jan 4, 2006·NeuroRx : the Journal of the American Society for Experimental NeuroTherapeutics·Tzu-Kang Sang, George R Jackson
Jul 26, 2013·Proceedings of the Japan Academy. Series B, Physical and Biological Sciences·Takaomi C Saido
Apr 1, 2009·International Journal of Molecular Sciences·Astrid Jeibmann, Werner Paulus
Nov 1, 2013·Evidence-based Complementary and Alternative Medicine : ECAM·Chun-Fai NgClara Bik-San Lau
Dec 15, 2011·Human Genetics·Miguel A Gama SosaGregory A Elder
Sep 15, 2012·Annual Review of Genetics·M JaiswalH J Bellen

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