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

Hye Yun Kim; Hyunjin Vincent Kim; Seonmi Jo; C. Justin Lee; Seon Young Choi; Dong Jin Kim; Youngsoo Kim

doi:10.1038/ncomms9997

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

Hye Yun Kim, Hyunjin Vincent Kim, Seonmi Jo, C. Justin Lee, Seon Young Choi, Dong Jin Kim, Youngsoo Kim

Department of Pharmacy

Research output: Contribution to journal › Article › peer-review

53 Citations (Scopus)

Abstract

Alzheimer's disease (AD) is characterized by the transition of amyloid-β (Aβ) monomers into toxic oligomers and plaques. Given that Aβ abnormality typically precedes the development of clinical symptoms, an agent capable of disaggregating existing Aβ aggregates may be advantageous. Here we report that a small molecule, 4-(2-hydroxyethyl)-1-piperazinepropanesulphonic acid (EPPS), binds to Aβ aggregates and converts them into monomers. The oral administration of EPPS substantially reduces hippocampus-dependent behavioural deficits, brain Aβ oligomer and plaque deposits, glial 3-aminobutyric acid (GABA) release and brain inflammation in an Aβ-overexpressing, APP/PS1 transgenic mouse model when initiated after the development of severe AD-like phenotypes. The ability of EPPS to rescue Aβ aggregation and behavioural deficits provides strong support for the view that the accumulation of Aβ is an important mechanism underlying AD.

Original language	English
Article number	8997
Journal	Nature communications
Volume	6
DOIs	https://doi.org/10.1038/ncomms9997
Publication status	Published - 2015 Dec 8

Bibliographical note

Funding Information:
This work was supported by Korea Institute of Science and Technology Institutional Programs (KIST 2E25023 and 2E24582) and KHIDI (HI14C0466). We thank Dr Jeiwon Cho (KIST) for behaviour test instruments, Dr Jun-Seok Lee (KIST) for Y-maze analysis programmes and GE Healthcare Korea/Japan for Biacore analyses. We thank Dr Eun-Mi Hur (KIST), Dr Dennis W. Choi (Stony Brook University), Rafa Tasneem (Wellesley University) and Dr Bruce Hirayama (UCLA) for editing advices. LTP studies were performed at BnH. The cover art was created and donated by Ms Na Yun Kim.

All Science Journal Classification (ASJC) codes

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)

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title = "EPPS rescues hippocampus-dependent cognitive deficits in APP/PS1 mice by disaggregation of amyloid-β oligomers and plaques",

abstract = "Alzheimer's disease (AD) is characterized by the transition of amyloid-β (Aβ) monomers into toxic oligomers and plaques. Given that Aβ abnormality typically precedes the development of clinical symptoms, an agent capable of disaggregating existing Aβ aggregates may be advantageous. Here we report that a small molecule, 4-(2-hydroxyethyl)-1-piperazinepropanesulphonic acid (EPPS), binds to Aβ aggregates and converts them into monomers. The oral administration of EPPS substantially reduces hippocampus-dependent behavioural deficits, brain Aβ oligomer and plaque deposits, glial 3-aminobutyric acid (GABA) release and brain inflammation in an Aβ-overexpressing, APP/PS1 transgenic mouse model when initiated after the development of severe AD-like phenotypes. The ability of EPPS to rescue Aβ aggregation and behavioural deficits provides strong support for the view that the accumulation of Aβ is an important mechanism underlying AD.",

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note = "Funding Information: This work was supported by Korea Institute of Science and Technology Institutional Programs (KIST 2E25023 and 2E24582) and KHIDI (HI14C0466). We thank Dr Jeiwon Cho (KIST) for behaviour test instruments, Dr Jun-Seok Lee (KIST) for Y-maze analysis programmes and GE Healthcare Korea/Japan for Biacore analyses. We thank Dr Eun-Mi Hur (KIST), Dr Dennis W. Choi (Stony Brook University), Rafa Tasneem (Wellesley University) and Dr Bruce Hirayama (UCLA) for editing advices. LTP studies were performed at BnH. The cover art was created and donated by Ms Na Yun Kim.",

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