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

Autor: Roland Benz, Martin Fuhrman, Hope Y Agbemenyah, Joon Lee, Lalit Kaurani, Gregor Eichele, Markus Zweckstetter, Gaurav Jain, Nasrollah Rezaei-Ghaleh, Andre Fischer, Alan L. Gillman, Gayane Grigorian, Ratnesh Lal, Sergey Ryazanov, Mario Caruana, Armin Giese, Christian Griesinger, Martin Korte, Eva Benito, Angelique Camilleri, Andrei Leonov, Neville Vassallo, Jens Wagner, Fernando Teran Arce, Hendrik Urbanke, Ana Martinez Hernandez, Anja Schneider, Petra Wilken
Rok vydání: 2018
Předmět:
0301 basic medicine
Male
3-(1
3-benzodioxol-5-yl)-5-(3-bromophenyl)-1H-pyrazole
Medicine (General)
drug effects [Hippocampus]
Hippocampus
genetics [Alzheimer Disease]
metabolism [Hippocampus]
Disease
Hippocampal formation
QH426-470
therapeutic use [Benzodioxoles]
Inbred C57BL
Medical and Health Sciences
Transcriptome
Mice
0302 clinical medicine
drug effects [Neuronal Plasticity]
drug therapy [Alzheimer Disease]
genetics [Amyloid beta-Peptides]
Amyloid beta-protein
Spatial Memory
Neuronal Plasticity
Alzheimer's disease -- Pathophysiology
membrane pores
Biological Sciences
Alzheimer's disease
Phenotype
3. Good health
Alzheimer's disease -- Treatment
drug effects [Transcriptome]
therapeutic use [Pyrazoles]
Molecular Medicine
drug effects [Spatial Memory]
A beta channels
metabolism [Alzheimer Disease]
metabolism [Amyloid beta-Peptides]
pharmacology [Benzodioxoles]
Aβ channels
physiopathology [Alzheimer Disease]
03 medical and health sciences
R5-920
Alzheimer Disease
Neuroplasticity
medicine
Genetics
Dementia
Animals
ddc:610
Benzodioxoles
Amyloid beta-Peptides
business.industry
Animal
medicine.disease
Mice
Inbred C57BL
Disease Models
Animal
030104 developmental biology
Alzheimers disease
Plaque
amyloid -- Physiopathology
Disease Models
physiopathology [Hippocampus]
gene expression
Pyrazoles
amyloid pathology
business
pharmacology [Pyrazoles]
Neuroscience
030217 neurology & neurosurgery
Nervous system -- Degeneration
Zdroj: EMBO Molecular Medicine
EMBO molecular medicine 10(1), 32-47 (2018). doi:10.15252/emmm.201707825
EMBO Molecular Medicine, Vol 10, Iss 1, Pp 32-47 (2018)
EMBO molecular medicine
EMBO molecular medicine, vol 10, iss 1
ISSN: 1757-4676
DOI: 10.15252/emmm.201707825
Popis: 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 Ab pores without changing the membrane embedded Ab-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.
peer-reviewed
Databáze: OpenAIRE
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