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

Martinez Hernandez, A., Urbanke, H., Gillman, A. L., Lee, J., Ryazanov, S., Agbemenyah, H. Y., et al. (2018). The diphenylpyrazole compound anle138b blocks Aβ channels and rescues disease phenotypes in a mouse model for amyloid pathology. EMBO Molecular Medicine, 10(1), 32-47. doi:10.15252/emmm.201707825.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002E-80AE-5 Version Permalink: http://hdl.handle.net/21.11116/0000-0001-30F3-6
Genre: Journal Article

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 Creators:
Martinez Hernandez, A.1, Author              
Urbanke, H., Author
Gillman, A. L., Author
Lee, J., Author
Ryazanov, S.2, Author              
Agbemenyah, H. Y., Author
Benito, E., Author
Jain, G., Author
Kaurani, L., Author
Grigorian, G., Author
Leonov, A.2, Author              
Rezaei-Ghaleh, N.3, Author              
Wilken, P., Author
Arce, F. T., Author
Wagner, J., Author
Fuhrman, M., Author
Caruana, M., Author
Camilleri, A., Author
Vassallo, N., Author
Zweckstetter, M.3, Author              
Benz, R., AuthorGiese, A., AuthorSchneider, A., AuthorKorte, M., AuthorLal, R., AuthorGriesinger, C.2, Author              Eichele, G.1, Author              Fischer, A., Author more..
Affiliations:
1Department of Genes and Behavior, MPI for biophysical chemistry, Max Planck Society, ou_persistent34              
2Department of NMR Based Structural Biology, MPI for biophysical chemistry, Max Planck Society, ou_578567              
3Research Group of Protein Structure Determination using NMR, MPI for biophysical chemistry, Max Planck Society, ou_578571              

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Free keywords: Alzheimer's disease; Aβ channels; amyloid pathology; gene expression; membrane pores
 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.

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Language(s): eng - English
 Dates: 2017-12-052018-01-01
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.15252/emmm.201707825
 Degree: -

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Title: EMBO Molecular Medicine
Source Genre: Journal
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Publ. Info: -
Pages: - Volume / Issue: 10 (1) Sequence Number: - Start / End Page: 32 - 47 Identifier: -