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

Research output: Contribution to journalArticle

41 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 languageEnglish
Article number8997
JournalNature communications
Volume6
DOIs
Publication statusPublished - 2015 Dec 8

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hippocampus
Amyloid Plaques
oligomers
Oligomers
Amyloid
mice
Hippocampus
Alzheimer Disease
acids
Acids
Brain
Monomers
brain
Aptitude
monomers
Poisons
Encephalitis
Neuroglia
Transgenic Mice
phenotype

All Science Journal Classification (ASJC) codes

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

Cite this

Kim, Hye Yun ; Kim, Hyunjin Vincent ; Jo, Seonmi ; Lee, C. Justin ; Choi, Seon Young ; Kim, Dong Jin ; Kim, YoungSoo. / EPPS rescues hippocampus-dependent cognitive deficits in APP/PS1 mice by disaggregation of amyloid-β oligomers and plaques. In: Nature communications. 2015 ; Vol. 6.
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EPPS rescues hippocampus-dependent cognitive deficits in APP/PS1 mice by disaggregation of amyloid-β oligomers and plaques. / Kim, Hye Yun; Kim, Hyunjin Vincent; Jo, Seonmi; Lee, C. Justin; Choi, Seon Young; Kim, Dong Jin; Kim, YoungSoo.

In: Nature communications, Vol. 6, 8997, 08.12.2015.

Research output: Contribution to journalArticle

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