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Article
Novel Neuroprotective Function of Apical-Basal Polarity GeneCrumbs in Amyloid Beta 42 (Aβ42) Mediated Neurodegeneration
PLOS One
  • Andrew Steffensmeier, University of Dayton
  • Meghana Tare, University of Dayton
  • Oorvashi Roy Puli, University of Dayton
  • Rohan Modi, University of Dayton
  • Jaison Nainaparampil, University of Dayton
  • Madhuri Kango-Singh, University of Dayton
  • Amit Singh, University of Dayton
Document Type
Article
Publication Date
11-1-2013
Abstract
Alzheimer's disease (AD, OMIM: 104300), a progressive neurodegenerative disorder with no cure to date, is caused by the generation of amyloid-beta-42 (Aβ42) aggregates that trigger neuronal cell death by unknown mechanism(s). We have developed a transgenic Drosophilaeye model where misexpression of human Aβ42 results in AD-like neuropathology in the neural retina. We have identified an apical-basal polarity gene crumbs (crb) as a genetic modifier of Aβ42-mediated-neuropathology. Misexpression of Aβ42 caused upregulation of Crb expression, whereas downregulation of Crb either by RNAi or null allele approach rescued the Aβ42-mediated-neurodegeneration. Co-expression of full length Crb with Aβ42 increased severity of Aβ42-mediated-neurodegeneration, due to three fold induction of cell death in comparison to the wild type. Higher Crb levels affect axonal targeting from the retina to the brain. The structure function analysis identified intracellular domain of Crb to be required for Aβ42-mediated-neurodegeneration. We demonstrate a novel neuroprotective role of Crb in Aβ42-mediated-neurodegeneration.
ISBN/ISSN
1932-6203
Document Version
Published Version
Comments

Permission documentation is on file.

Publisher
PLOS One
Peer Reviewed
Yes
Citation Information
Andrew Steffensmeier, Meghana Tare, Oorvashi Roy Puli, Rohan Modi, et al.. "Novel Neuroprotective Function of Apical-Basal Polarity GeneCrumbs in Amyloid Beta 42 (Aβ42) Mediated Neurodegeneration" PLOS One Vol. 8 Iss. 18 (2013)
Available at: http://works.bepress.com/amit_singh/14/