EPPS rescues hippocampus-dependent cognitive deficits in APP/PS1 mice by disaggregation of amyloid-b oligomers and plaques

Title
EPPS rescues hippocampus-dependent cognitive deficits in APP/PS1 mice by disaggregation of amyloid-b oligomers and plaques
Authors
김혜연김현진조선미이창준최선영김동진김영수
Keywords
알츠하이머; 치매; 치료제; Alzheimer; Dementia; drug discovery
Issue Date
2015-12
Publisher
Nature Communications
Citation
VOL 6, NO 8997, 1-12
Abstract
Alzheimer’s disease (AD) is characterized by the transition of amyloid-b (Ab) monomers into toxic oligomers and plaques. Given that Ab abnormality typically precedes the development of clinical symptoms, an agent capable of disaggregating existing Ab aggregates may be advantageous. Here we report that a small molecule, 4-(2-hydroxyethyl)-1-piperazinepropanesulphonic acid (EPPS), binds to Ab aggregates and converts them into monomers. The oral administration of EPPS substantially reduces hippocampus-dependent behavioural deficits, brain Ab oligomer and plaque deposits, glial g-aminobutyric acid (GABA) release and brain inflammation in an Ab-overexpressing, APP/PS1 transgenic mouse model when initiated after the development of severe AD-like phenotypes. The ability of EPPS to rescue Ab aggregation and behavioural deficits provides strong support for the view that the accumulation of Ab is an important mechanism underlying AD.
URI
http://pubs.kist.re.kr/handle/201004/58257
ISSN
20411723
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KIST Publication > Article
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