Apolipoprotein E-Mimetics Inhibit Neurodegeneration and Restore Cognitive Functions in a Transgenic Drosophila Model of Alzheimer's Disease |
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| Authors: | Svetlana Sarantseva Svetlana Timoshenko Olga Bolshakova Eugenia Karaseva Dmitry Rodin Alexander L Schwarzman Michael P Vitek |
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| Institution: | 1. Petersburg Institute of Nuclear Physics, Russian Academy of Sciences, Gatchina, Russia.; 2. Institute for Experimental Medicine, Russian Academy of Medical Sciences, St. Petersburg, Russia.; 3. Division of Neurology, Duke University Medical Center, Durham, North Carolina, United States of America.; 4. Cognosci, Inc., Research Triangle Park, North Carolina, United States of America.;Massachusetts General Hospital and Harvard Medical School, United States of America |
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| Abstract: | BackgroundMutations of the amyloid precursor protein gene (APP) are found in familial forms of Alzheimer''s disease (AD) and some lead to the elevated production of amyloid-β-protein (Aβ). While Aβ has been implicated in the causation of AD, the exact role played by Aβ and its APP precursor are still unclear.Principal FindingsIn our study, Drosophila melanogaster transgenics were established as a model to analyze AD-like pathology caused by APP overexpression. We demonstrated that age related changes in the levels and pattern of synaptic proteins accompanied progressive neurodegeneration and impairment of cognitive functions in APP transgenic flies, but that these changes may be independent from the generation of Aβ. Using novel peptide mimetics of Apolipoprotein-E, COG112 or COG133 proved to be neuroprotective and significantly improved the learning and memory of APP transgenic flies.ConclusionsThe development of neurodegeneration and cognitive deficits was corrected by injections of COG112 or COG133, novel mimetics of apolipoprotein-E (apoE) with neuroprotective activities. |
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