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The diphenylpyrazole compound anle138b blocks Aß 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; Fuhrmann, 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.
Afiliação
  • Martinez Hernandez A; Department for Epigenetics and Systems Medicine in Neurodegenerative Diseases, German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany.
  • Urbanke H; Department for Genes and Behavior, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
  • Gillman AL; Department for Epigenetics and Systems Medicine in Neurodegenerative Diseases, German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany.
  • Lee J; Department of Bioengineering, Materials Science and Engineering, Department of Mechanical and Aerospace Engineering and Institute of Engineering in Medicine, University of California San Diego, La Jolla, CA, USA.
  • Ryazanov S; Department of Bioengineering, Materials Science and Engineering, Department of Mechanical and Aerospace Engineering and Institute of Engineering in Medicine, University of California San Diego, La Jolla, CA, USA.
  • Agbemenyah HY; Department of NMR Based Structural Biology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
  • Benito E; DFG Research Center Nanoscale Microscopy and Molecular Physiology of the Brain, Göttingen, Germany.
  • Jain G; Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany.
  • Kaurani L; Department for Epigenetics and Systems Medicine in Neurodegenerative Diseases, German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany.
  • Grigorian G; Department for Epigenetics and Systems Medicine in Neurodegenerative Diseases, German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany.
  • Leonov A; DFG Research Center Nanoscale Microscopy and Molecular Physiology of the Brain, Göttingen, Germany.
  • Rezaei-Ghaleh N; Department of Cellular Neurobiology, Technical University Braunschweig, Braunschweig, Germany.
  • Wilken P; Department of NMR Based Structural Biology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
  • Arce FT; DFG Research Center Nanoscale Microscopy and Molecular Physiology of the Brain, Göttingen, Germany.
  • Wagner J; Department of NMR Based Structural Biology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
  • Fuhrmann M; Department of Translational Structural Biology of Dementia, German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany.
  • Caruana M; DFG Research Center Nanoscale Microscopy and Molecular Physiology of the Brain, Göttingen, Germany.
  • Camilleri A; Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany.
  • Vassallo N; Group for Translational Research in Neurodegenerative Diseases, German Center for Neurodegenerative Diseases (DZNE) Göttingen, Göttingen, Germany.
  • Zweckstetter M; Department of Bioengineering, Materials Science and Engineering, Department of Mechanical and Aerospace Engineering and Institute of Engineering in Medicine, University of California San Diego, La Jolla, CA, USA.
  • Benz R; Group for Neuroimmunology and Imaging, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
  • Giese A; Group for Neuroimmunology and Imaging, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
  • Schneider A; Department of Physiology and Biochemistry, Centre for Molecular Medicine and Biobanking, University of Malta, Msida, Malta.
  • Korte M; Department of Physiology and Biochemistry, Centre for Molecular Medicine and Biobanking, University of Malta, Msida, Malta.
  • Lal R; Department of Physiology and Biochemistry, Centre for Molecular Medicine and Biobanking, University of Malta, Msida, Malta.
  • Griesinger C; Department of NMR Based Structural Biology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
  • Eichele G; DFG Research Center Nanoscale Microscopy and Molecular Physiology of the Brain, Göttingen, Germany.
  • Fischer A; Department of Translational Structural Biology of Dementia, German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany.
EMBO Mol Med ; 10(1): 32-47, 2018 01.
Article em En | MEDLINE | ID: mdl-29208638
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 Aß pores without changing the membrane embedded Aß-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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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Pirazóis / Peptídeos beta-Amiloides / Benzodioxóis / Doença de Alzheimer / Hipocampo Limite: Animals Idioma: En Ano de publicação: 2018 Tipo de documento: Article
Texto completo
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XML
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Pirazóis / Peptídeos beta-Amiloides / Benzodioxóis / Doença de Alzheimer / Hipocampo Limite: Animals Idioma: En Ano de publicação: 2018 Tipo de documento: Article