Kim, Hye Yun Kim, Hyunjin Vincent Jo, Seonmi Lee, C. Justin Choi, Seon Young Kim, Dong Jin Kim, YoungSoo 2024-01-20T05:32:39Z 2024-01-20T05:32:39Z 2021-09-03 2015-12 2041-1723 https://pubs.kist.re.kr/handle/201004/124711 Alzheimer's disease (AD) is characterized by the transition of amyloid-beta (A beta) monomers into toxic oligomers and plaques. Given that A beta abnormality typically precedes the development of clinical symptoms, an agent capable of disaggregating existing A beta aggregates may be advantageous. Here we report that a small molecule, 4-(2-hydroxyethyl)-1piperazinepropanesulphonic acid (EPPS), binds to A beta aggregates and converts them into monomers. The oral administration of EPPS substantially reduces hippocampus-dependent behavioural deficits, brain A beta oligomer and plaque deposits, glial gamma-aminobutyric acid (GABA) release and brain inflammation in an A beta-overexpressing, APP/PS1 transgenic mouse model when initiated after the development of severe AD-like phenotypes. The ability of EPPS to rescue A beta aggregation and behavioural deficits provides strong support for the view that the accumulation of A beta is an important mechanism underlying AD. English NATURE PUBLISHING GROUP EPPS rescues hippocampus-dependent cognitive deficits in APP/PS1 mice by disaggregation of amyloid-beta oligomers and plaques Article 10.1038/ncomms9997 1 NATURE COMMUNICATIONS, v.6 NATURE COMMUNICATIONS 6 N scie scopus 000367579100003 2-s2.0-84949599389 Multidisciplinary Sciences Science & Technology - Other Topics Article ALZHEIMERS-DISEASE A-BETA IN-VITRO SYNAPTIC PLASTICITY MEMORY AGGREGATION INHIBITORS TOXICITY STRATEGIES DONEPEZIL 알츠하이머 치매 치료제 Alzheimer Dementia drug discovery