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

2017-12-05 | journal article

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​The diphenylpyrazole compound anle138b blocks Aβ channels and rescues disease phenotypes in a mouse model for amyloid pathology​
Martinez-Hernandez, A. ; Urbanke, H. ; Gillman, A. L.; Lee, J.; Ryazanov, S. ; Agbemenyah, H. Y.   & Benito, E.  et al.​ (2017) 
EMBO molecular medicine10(1) pp. 32​-47​.​ DOI: https://doi.org/10.15252/emmm.201707825 

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Authors
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; Teran Arce, Fernando; Wagner, Jens ; Fuhrman, 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 
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.
Issue Date
5-December-2017
Journal
EMBO molecular medicine 
eISSN
1757-4684
Language
English

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