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.; Benito, E.; Jain, G.; Kaurani, L.; Grigorian, G.; Leonov, A.; Rezaei-Ghaleh, N.; Wilken, P.; Arce, F. T.; Wagner, J.; Fuhrman, M.; Caruana, M.; Camilleri, A.; Vassallo, N.; Zweckstetter, M.; Benz, R.; Giese, A.; Schneider, A.; Korte, M.; Lal, R.; Griesinger, C.; Eichele, G.; Fischer, A.

doi:10.15252/emmm.201707825

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

MPS-Authors

/persons/resource/persons15217

Martinez Hernandez, A.
Department of Genes and Behavior, MPI for biophysical chemistry, Max Planck Society;

/persons/resource/persons45923

Ryazanov, S.
Department of NMR Based Structural Biology, MPI for biophysical chemistry, Max Planck Society;

/persons/resource/persons15438

Leonov, A.
Department of NMR Based Structural Biology, MPI for biophysical chemistry, Max Planck Society;

/persons/resource/persons36515

Rezaei-Ghaleh, N.
Research Group of Protein Structure Determination using NMR, MPI for biophysical chemistry, Max Planck Society;

/persons/resource/persons16093

Zweckstetter, M.
Research Group of Protein Structure Determination using NMR, MPI for biophysical chemistry, Max Planck Society;

/persons/resource/persons15147

Griesinger, C.
Department of NMR Based Structural Biology, MPI for biophysical chemistry, Max Planck Society;

/persons/resource/persons15030

Eichele, G.
Department of Genes and Behavior, MPI for biophysical chemistry, Max Planck Society;

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2508692.pdf
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2508692_Suppl_1.pdf
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2508692_Suppl_2.pdf
(付録資料), 430KB

2508692_Suppl_3.xlsx
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引用

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

引用: https://hdl.handle.net/11858/00-001M-0000-002E-80AE-5

要旨

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.