title: Novel neuroprotective function of apical-basal polarity gene crumbs in amyloid beta 42 (aβ42) mediated neurodegeneration.
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 Drosophila eye 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.
authors.affiliation: Premedical Program, University of Dayton, Dayton, Ohio, United States of America.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Steffensmeier
authors.forename: Meghana
authors.initials: M
authors.lastname: Tare
authors.forename: Oorvashi Roy
authors.initials: OR
authors.lastname: Puli
authors.forename: Rohan
authors.initials: R
authors.lastname: Modi
authors.forename: Jaison
authors.initials: J
authors.lastname: Nainaparampil
authors.forename: Madhuri
authors.initials: M
authors.lastname: Kango-Singh
authors.forename: Amit
authors.initials: A
authors.lastname: Singh
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship
chemical_list: D016229:Amyloid beta-Peptides; D029721:Drosophila Proteins; D008565:Membrane Proteins; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); C064360:crb protein, Drosophila