TY  - JOUR
AU  - Martinez Hernandez, Ana
AU  - Urbanke, Hendrik
AU  - Gillman, Alan L
AU  - Lee, Joon
AU  - Ryazanov, Sergey
AU  - Agbemenyah, Hope Y
AU  - Benito, Eva
AU  - Jain, Gaurav
AU  - Kaurani, Lalit
AU  - Grigorian, Gayane
AU  - Leonov, Andrei
AU  - Rezaei-Ghaleh, Nasrollah
AU  - Wilken, Petra
AU  - Arce, Fernando Teran
AU  - Wagner, Jens
AU  - Fuhrmann, Martin
AU  - Caruana, Mario
AU  - Camilleri, Angelique
AU  - Vassallo, Neville
AU  - Zweckstetter, Markus
AU  - Benz, Roland
AU  - Giese, Armin
AU  - Schneider, Anja
AU  - Korte, Martin
AU  - Lal, Ratnesh
AU  - Griesinger, Christian
AU  - Eichele, Gregor
AU  - Fischer, Andre
TI  - The diphenylpyrazole compound anle138b blocks Aβ channels and rescues disease phenotypes in a mouse model for amyloid pathology.
JO  - EMBO molecular medicine
VL  - 10
IS  - 1
SN  - 1757-4676
CY  - Heidelberg
PB  - EMBO Press
M1  - DZNE-2020-06044
SP  - 32-47
PY  - 2018
AB  - 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.
KW  - Alzheimer Disease: drug therapy
KW  - Alzheimer Disease: genetics
KW  - Alzheimer Disease: metabolism
KW  - Alzheimer Disease: physiopathology
KW  - Amyloid beta-Peptides: genetics
KW  - Amyloid beta-Peptides: metabolism
KW  - Animals
KW  - Benzodioxoles: pharmacology
KW  - Benzodioxoles: therapeutic use
KW  - Disease Models, Animal
KW  - Hippocampus: drug effects
KW  - Hippocampus: metabolism
KW  - Hippocampus: physiopathology
KW  - Male
KW  - Mice
KW  - Mice, Inbred C57BL
KW  - Neuronal Plasticity: drug effects
KW  - Phenotype
KW  - Pyrazoles: pharmacology
KW  - Pyrazoles: therapeutic use
KW  - Spatial Memory: drug effects
KW  - Transcriptome: drug effects
KW  - 3-(1,3-benzodioxol-5-yl)-5-(3-bromophenyl)-1H-pyrazole (NLM Chemicals)
KW  - Amyloid beta-Peptides (NLM Chemicals)
KW  - Benzodioxoles (NLM Chemicals)
KW  - Pyrazoles (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:29208638
C2  - pmc:PMC5760857
DO  - DOI:10.15252/emmm.201707825
UR  - https://pub.dzne.de/record/139722
ER  -