Novel Neuroprotective Function of Apical-Basal Polarity GeneCrumbs in Amyloid Beta 42 (Aβ42) Mediated Neurodegeneration

Author(s)

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 DaytonFollow
Amit Singh, University of DaytonFollow

Document Type

Article

Publication Date

11-2013

Publication Source

PLOS One

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.

Copyright

Copyright © 2013, Steffensmeier et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Publisher

PLOS One

Volume

8

Peer Reviewed

yes

Issue

18

eCommons Citation

Steffensmeier, Andrew; Tare, Meghana; Puli, Oorvashi Roy; Modi, Rohan; Nainaparampil, Jaison; Kango-Singh, Madhuri; and Singh, Amit, "Novel Neuroprotective Function of Apical-Basal Polarity GeneCrumbs in Amyloid Beta 42 (Aβ42) Mediated Neurodegeneration" (2013). Biology Faculty Publications. 128.
https://ecommons.udayton.edu/bio_fac_pub/128