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

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...

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Detalles Bibliográficos
Autores principales: 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, 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5760857/
https://www.ncbi.nlm.nih.gov/pubmed/29208638
http://dx.doi.org/10.15252/emmm.201707825
Descripción
Sumario: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.