Apolipoprotein E-mimetics inhibit neurodegeneration and restore cognitive functions in a transgenic Drosophila model of Alzheimer's disease.
BACKGROUND
Mutations 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-beta-protein (Abeta). While Abeta has been implicated in the causation of AD, the exact role played by Abeta and its APP precursor are still unclear.


RESULTS
In 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 Abeta. 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.


CONCLUSIONS
The development of neurodegeneration and cognitive deficits was corrected by injections of COG112 or COG133, novel mimetics of apolipoprotein-E (apoE) with neuroprotective activities.
Sarantseva
Svetlana
S
Petersburg Institute of Nuclear Physics, Russian Academy of Sciences, Gatchina, Russia.
Timoshenko
Svetlana
S
Bolshakova
Olga
O
Karaseva
Eugenia
E
Rodin
Dmitry
D
Schwarzman
Alexander L
AL
Vitek
Michael P
MP
D000375:Aging / Q000187:drug effects / Q000473:pathology; D000544:Alzheimer Disease / Q000150:complications / Q000188:drug therapy / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D001057:Apolipoproteins E / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003071:Cognition / Q000187:drug effects*; D004195:Disease Models, Animal; D004331:Drosophila melanogaster / Q000187:drug effects* / Q000235:genetics*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D008568:Memory / Q000187:drug effects; D009410:Nerve Degeneration / Q000150:complications / Q000188:drug therapy / Q000517:prevention & control*; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D050683:R-SNARE Proteins / Q000378:metabolism
D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; C530207:COG112 peptide; D010455:Peptides; D050683:R-SNARE Proteins; D049452:Green Fluorescent Proteins