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The diphenylpyrazole compound anle138b blocks Aβ channels and rescues disease phenotypes in a mouse model for amyloid pathology
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...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
John Wiley and Sons Inc.
2017
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5760857/ https://www.ncbi.nlm.nih.gov/pubmed/29208638 http://dx.doi.org/10.15252/emmm.201707825 |
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| author | Martinez Hernandez, Ana Urbanke, Hendrik Gillman, Alan L Lee, Joon Ryazanov, Sergey Agbemenyah, Hope Y Benito, Eva Jain, Gaurav Kaurani, Lalit Grigorian, Gayane Leonov, Andrei Rezaei‐Ghaleh, Nasrollah Wilken, Petra Arce, Fernando Teran Wagner, Jens Fuhrman, Martin Caruana, Mario Camilleri, Angelique Vassallo, Neville Zweckstetter, Markus Benz, Roland Giese, Armin Schneider, Anja Korte, Martin Lal, Ratnesh Griesinger, Christian Eichele, Gregor Fischer, Andre |
| author_facet | Martinez Hernandez, Ana Urbanke, Hendrik Gillman, Alan L Lee, Joon Ryazanov, Sergey Agbemenyah, Hope Y Benito, Eva Jain, Gaurav Kaurani, Lalit Grigorian, Gayane Leonov, Andrei Rezaei‐Ghaleh, Nasrollah Wilken, Petra Arce, Fernando Teran Wagner, Jens Fuhrman, Martin Caruana, Mario Camilleri, Angelique Vassallo, Neville Zweckstetter, Markus Benz, Roland Giese, Armin Schneider, Anja Korte, Martin Lal, Ratnesh Griesinger, Christian Eichele, Gregor Fischer, Andre |
| author_sort | Martinez Hernandez, Ana |
| collection | PubMed |
| description | 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. |
| format | Online Article Text |
| id | pubmed-5760857 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2017 |
| publisher | John Wiley and Sons Inc. |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-57608572018-01-10 The diphenylpyrazole compound anle138b blocks Aβ channels and rescues disease phenotypes in a mouse model for amyloid pathology Martinez Hernandez, Ana Urbanke, Hendrik Gillman, Alan L Lee, Joon Ryazanov, Sergey Agbemenyah, Hope Y Benito, Eva Jain, Gaurav Kaurani, Lalit Grigorian, Gayane Leonov, Andrei Rezaei‐Ghaleh, Nasrollah Wilken, Petra Arce, Fernando Teran Wagner, Jens Fuhrman, Martin Caruana, Mario Camilleri, Angelique Vassallo, Neville Zweckstetter, Markus Benz, Roland Giese, Armin Schneider, Anja Korte, Martin Lal, Ratnesh Griesinger, Christian Eichele, Gregor Fischer, Andre EMBO Mol Med Research Articles 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. John Wiley and Sons Inc. 2017-12-05 2018-01 /pmc/articles/PMC5760857/ /pubmed/29208638 http://dx.doi.org/10.15252/emmm.201707825 Text en © 2017 The Authors. Published under the terms of the CC BY 4.0 license This is an open access article under the terms of the Creative Commons Attribution 4.0 (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
| spellingShingle | Research Articles Martinez Hernandez, Ana Urbanke, Hendrik Gillman, Alan L Lee, Joon Ryazanov, Sergey Agbemenyah, Hope Y Benito, Eva Jain, Gaurav Kaurani, Lalit Grigorian, Gayane Leonov, Andrei Rezaei‐Ghaleh, Nasrollah Wilken, Petra Arce, Fernando Teran Wagner, Jens Fuhrman, Martin Caruana, Mario Camilleri, Angelique Vassallo, Neville Zweckstetter, Markus Benz, Roland Giese, Armin Schneider, Anja Korte, Martin Lal, Ratnesh Griesinger, Christian Eichele, Gregor Fischer, Andre The diphenylpyrazole compound anle138b blocks Aβ channels and rescues disease phenotypes in a mouse model for amyloid pathology |
| title | The diphenylpyrazole compound anle138b blocks Aβ channels and rescues disease phenotypes in a mouse model for amyloid pathology |
| title_full | The diphenylpyrazole compound anle138b blocks Aβ channels and rescues disease phenotypes in a mouse model for amyloid pathology |
| title_fullStr | The diphenylpyrazole compound anle138b blocks Aβ channels and rescues disease phenotypes in a mouse model for amyloid pathology |
| title_full_unstemmed | The diphenylpyrazole compound anle138b blocks Aβ channels and rescues disease phenotypes in a mouse model for amyloid pathology |
| title_short | The diphenylpyrazole compound anle138b blocks Aβ channels and rescues disease phenotypes in a mouse model for amyloid pathology |
| title_sort | diphenylpyrazole compound anle138b blocks aβ channels and rescues disease phenotypes in a mouse model for amyloid pathology |
| topic | Research Articles |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5760857/ https://www.ncbi.nlm.nih.gov/pubmed/29208638 http://dx.doi.org/10.15252/emmm.201707825 |
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