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

dc.contributor.authorMartinez Hernandez, Ana
dc.contributor.authorUrbanke, Hendrik
dc.contributor.authorGillman, Alan L
dc.contributor.authorLee, Joon
dc.contributor.authorRyazanov, Sergey
dc.contributor.authorAgbemenyah, Hope Y
dc.contributor.authorBenito, Eva
dc.contributor.authorJain, Gaurav
dc.contributor.authorKaurani, Lalit
dc.contributor.authorGrigorian, Gayane
dc.contributor.authorLeonov, Andrei
dc.contributor.authorRezaei‐Ghaleh, Nasrollah
dc.contributor.authorWilken, Petra
dc.contributor.authorArce, Fernando Teran
dc.contributor.authorWagner, Jens
dc.contributor.authorFuhrman, Martin
dc.contributor.authorCaruana, Mario
dc.contributor.authorCamilleri, Angelique
dc.contributor.authorVassallo, Neville
dc.contributor.authorZweckstetter, Markus
dc.contributor.authorBenz, Roland
dc.contributor.authorGiese, Armin
dc.contributor.authorSchneider, Anja
dc.contributor.authorKorte, Martin
dc.contributor.authorLal, Ratnesh
dc.contributor.authorGriesinger, Christian
dc.contributor.authorEichele, Gregor
dc.contributor.authorFischer, Andre
dc.date.accessioned2018-02-16T16:33:09Z
dc.date.available2018-02-16T16:33:09Z
dc.date.issued2018-01
dc.identifier.citationThe diphenylpyrazole compound anle138b blocks Aβ channels and rescues disease phenotypes in a mouse model for amyloid pathology 2018, 10 (1):32 EMBO Molecular Medicineen
dc.identifier.issn1757-4676
dc.identifier.issn1757-4684
dc.identifier.pmid29208638
dc.identifier.doi10.15252/emmm.201707825
dc.identifier.urihttp://hdl.handle.net/10150/626613
dc.description.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.
dc.description.sponsorshipDZNE; 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]en
dc.language.isoenen
dc.publisherWILEYen
dc.relation.urlhttp://embomolmed.embopress.org/lookup/doi/10.15252/emmm.201707825en
dc.rights© 2017 The Authors. Published under the terms of the CC BY 4.0 license.en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectAlzheimer's diseaseen
dc.subjectamyloid pathologyen
dc.subjectA beta channelsen
dc.subjectgene expressionen
dc.subjectmembrane poresen
dc.titleThe diphenylpyrazole compound anle138b blocks Aβ channels and rescues disease phenotypes in a mouse model for amyloid pathologyen
dc.typeArticleen
dc.contributor.departmentUniv Arizona, Dept Meden
dc.contributor.departmentUniv Arizona, Dept Biomed Engnen
dc.identifier.journalEMBO Molecular Medicineen
dc.description.noteOpen access journal.en
dc.description.collectioninformationThis 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 repository@u.library.arizona.edu.en
dc.eprint.versionFinal published versionen
refterms.dateFOA2018-06-16T20:55:04Z
html.description.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.


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© 2017 The Authors. Published under the terms of the CC BY 4.0 license.
Except where otherwise noted, this item's license is described as © 2017 The Authors. Published under the terms of the CC BY 4.0 license.