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

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

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