Open AccessThe 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,
RezaeiGhaleh 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
Publication year - 2018
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201707825
Subject(s) - phenotype , amyloid (mycology) , pathology , biology , disease , clinical phenotype , microbiology and biotechnology , medicine , genetics , gene
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.