Journal Article

DZNE-2020-06044

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png The diphenylpyrazole compound anle138b blocks Aβ channels and rescues disease phenotypes in a mouse model for amyloid pathology.

Martinez Hernandez, A. (First author)DZNE* ; Urbanke, H.DZNE* ; Gillman, A. L. ; Lee, J. ; Ryazanov, S. ; Agbemenyah, H. Y. ; Benito, E.DZNE* ; Jain, G.DZNE* ; Kaurani, L. ; Grigorian, G. ; Leonov, A. ; Rezaei-Ghaleh, N.DZNE* ; Wilken, P.DZNE* ; Arce, F. T. ; Wagner, J.DZNE* ; Fuhrmann, M.DZNE* ; Caruana, M. ; Camilleri, A. ; Vassallo, N. ; Zweckstetter, M.DZNE* ; Benz, R. ; Giese, A. ; Schneider, A.DZNE* ; Korte, M. (Corresponding author) ; Lal, R. ; Griesinger, C. ; Eichele, G. ; Fischer, A. (Last author)DZNE*

2018
EMBO Press Heidelberg

This record in other databases:    

Please use a persistent id in citations: doi:10.15252/emmm.201707825

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.

Keyword(s): Alzheimer Disease: drug therapy (MeSH) ; Alzheimer Disease: genetics (MeSH) ; Alzheimer Disease: metabolism (MeSH) ; Alzheimer Disease: physiopathology (MeSH) ; Amyloid beta-Peptides: genetics (MeSH) ; Amyloid beta-Peptides: metabolism (MeSH) ; Animals (MeSH) ; Benzodioxoles: pharmacology (MeSH) ; Benzodioxoles: therapeutic use (MeSH) ; Disease Models, Animal (MeSH) ; Hippocampus: drug effects (MeSH) ; Hippocampus: metabolism (MeSH) ; Hippocampus: physiopathology (MeSH) ; Male (MeSH) ; Mice (MeSH) ; Mice, Inbred C57BL (MeSH) ; Neuronal Plasticity: drug effects (MeSH) ; Phenotype (MeSH) ; Pyrazoles: pharmacology (MeSH) ; Pyrazoles: therapeutic use (MeSH) ; Spatial Memory: drug effects (MeSH) ; Transcriptome: drug effects (MeSH) ; 3-(1,3-benzodioxol-5-yl)-5-(3-bromophenyl)-1H-pyrazole ; Amyloid beta-Peptides ; Benzodioxoles ; Pyrazoles

---

Contributing Institute(s):

1. Epigenetics and Systems Medicine in Neurodegenerative Diseases (AG Fischer ; AG Fischer)
2. Translational Structural Biology (AG Zweckstetter)
3. Neuroimmunology and Imaging (AG Fuhrmann)
4. Translational Dementia Research Göttingen (AG Schneider Göttingen)

Research Program(s):

1. 342 - Disease Mechanisms and Model Systems (POF3-342) (POF3-342)
2. 344 - Clinical and Health Care Research (POF3-344) (POF3-344)

Appears in the scientific report 2018

---

Database coverage:
; ; ; ; BIOSIS Previews ; Clarivate Analytics Master Journal List ; DOAJ Seal ; IF >= 10 ; JCR ; SCOPUS ; Web of Science Core Collection

---