The diphenylpyrazole compound anle138b blocks Aβ channels and rescues disease phenotypes in a mouse model for amyloid pathology
AuthorMartinez Hernandez, Ana
Gillman, Alan L
Agbemenyah, Hope Y
Arce, Fernando Teran
AffiliationUniv Arizona, Dept Med
Univ Arizona, Dept Biomed Engn
MetadataShow full item record
CitationThe diphenylpyrazole compound anle138b blocks Aβ channels and rescues disease phenotypes in a mouse model for amyloid pathology 2018, 10 (1):32 EMBO Molecular Medicine
JournalEMBO Molecular Medicine
Rights© 2017 The Authors. Published under the terms of the CC BY 4.0 license.
Collection InformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at firstname.lastname@example.org.
AbstractAlzheimer'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 Ab pores without changing the membrane embedded A beta-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.
NoteOpen access journal.
VersionFinal published version
SponsorsDZNE; Max Planck Society; Hans and Ilse Breuer Award for Alzheimer's disease; DFG [FI981/9-1, SFB803]; EU (ERC); Hans and Ilse Breuer Foundation; CoEN Initiative [CoEN3018]; Malta Council for Science & Technology through the National Research & Innovation Programme [RI-2008-068]; University of Malta [PHBR06]; Malta Government Scholarship Scheme; National Institute on Aging of National Institutes of Health [AG028709]; [SFB1089 C01]