The diphenylpyrazole compound anle138b blocks Aβ channels and rescues disease phenotypes in a mouse model for amyloid pathology

Ana Martinez Hernandez, Hendrik Urbanke, Alan L. Gillman, Joon Lee, Sergey Ryazanov, Hope Y. Agbemenyah, Eva Benito, Gaurav Jain, Lalit Kaurani, Gayane Grigorian, Andrei Leonov, Nasrollah Rezaei-Ghaleh, Petra Wilken, Fernando Teran Arce, Jens Wagner, Martin Fuhrman, Mario Caruana, Angelique Camilleri, Neville Vassallo, Markus ZweckstetterRoland Benz, Armin Giese, Anja Schneider, Martin Korte, Ratnesh Lal, Christian Griesinger, Gregor Eichele, Andre Fischer

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

Alzheimer's disease is a devastating neurodegenerative disease eventually leading to dementia. An effective treatment does not yet exist. Here we show that oral application of the compound anle138b restores hippocampal synaptic and transcriptional plasticity as well as spatial memory in a mouse model for Alzheimer's disease, when given orally before or after the onset of pathology. At the mechanistic level, we provide evidence that anle138b blocks the activity of conducting Aβ pores without changing the membrane embedded Aβ-oligomer structure. In conclusion, our data suggest that anle138b is a novel and promising compound to treat AD-related pathology that should be investigated further.

Original languageEnglish (US)
Pages (from-to)32-47
Number of pages16
JournalEMBO Molecular Medicine
Volume10
Issue number1
DOIs
StatePublished - Jan 2018

Keywords

  • Alzheimer's disease
  • Aβ channels
  • amyloid pathology
  • gene expression
  • membrane pores

ASJC Scopus subject areas

  • Molecular Medicine

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