Alzheimer’s disease; autophagic flux; neurodegeneration; phosphorylated Aβ; post-translationally modified Aβ; vesicular trafficking; Amyloid beta-Peptides; Green Fluorescent Proteins; Serine; Phosphorylation; Green Fluorescent Proteins/metabolism; Lysosomes/metabolism; Autophagy/physiology; Amyloid beta-Peptides/metabolism; Autophagy; Lysosomes; Molecular Biology; Cell Biology; phosphorylated A beta; post-translationally modified A beta
Abstract :
[en] AD: Alzheimer disease; APP: amyloid beta precursor protein; ATG: autophagy related; Aβ: amyloid-β; CTSD: cathepsin D; DAPI: 4',6-diamidino-2-phenylindole; EEA1: early endosome antigen 1; FA: formic acid; GFP: green fluorescent protein; LAMP2: lysosomal-associated membrane protein 2; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MAP2: microtubule-associated protein 2; nmAβ: non-modified amyloid-β; npAβ: non-phosphorylated amyloid-β; pAβ: phosphorylated amyloid-β; p-Ser26Aβ: amyloid-β phosphorylated at serine residue 26; p-Ser8Aβ: amyloid-β phosphorylated at serine residue 8; RAB: RAB, member RAS oncogene family; RFP: red fluorescent protein; SQSTM1/p62: sequestome 1; YFP: yellow fluorescent protein.
Disciplines :
Neurology
Author, co-author :
Kapadia, Akshay; Molecular Cell Biology, Department of Neurology, University Hospital Bonn, Bonn, Germany
Theil, Sandra; Molecular Cell Biology, Department of Neurology, University Hospital Bonn, Bonn, Germany
Opitz, Sabine; Neuroinflammation Unit, German Center for Neurodegenerative Diseases e. V. (DZNE), Bonn, Germany ; Section for Translational Epilepsy Research, Department of Neuropathology, University Hospital Bonn, Bonn, Germany
Villacampa, Nàdia; Neuroinflammation Unit, German Center for Neurodegenerative Diseases e. V. (DZNE), Bonn, Germany
Beckert, Hannes; Microscopy core facility, University Hospital Bonn, Bonn, Germany
Schoch, Susanne; Section for Translational Epilepsy Research, Department of Neuropathology, University Hospital Bonn, Bonn, Germany
HENEKA, Michael ; Neuroinflammation Unit, German Center for Neurodegenerative Diseases e. V. (DZNE), Bonn, Germany ; Department of Neurodegenerative Disease and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany
Kumar, Sathish; Molecular Cell Biology, Department of Neurology, University Hospital Bonn, Bonn, Germany
Walter, Jochen ; Molecular Cell Biology, Department of Neurology, University Hospital Bonn, Bonn, Germany
External co-authors :
yes
Language :
English
Title :
Phosphorylation-state dependent intraneuronal sorting of Aβ differentially impairs autophagy and the endo-lysosomal system.
Alzheimer Forschung Initiative e.V Alzheimer Forschung Initiative e.V Alzheimer Forschung Initiative e.V Deutsche Forschungsgemeinschaft Deutsche Forschungsgemeinschaft
Funding text :
The work was supported by the Alzheimer Forschung Initiative e.V. [12854]; Alzheimer Forschung Initiative e.V. [17011]; Alzheimer Forschung Initiative e.V. [T1803]; Deutsche Forschungsgemeinschaft [WA1477/6-6]; Deutsche Forschungsgemeinschaft [WA1477/6-3]. The authors would like to thank T. Bajaj and Dr. N. Gassen (University Clinic Bonn), and Dr. J. Höhfeld (University of Bonn) for sharing GFP-LC3-LC3Δ-RFP and mCherry-GFP-LC3B reporter cDNA constructs, scientific discussions, and result interpretation. The monoclonal antibodies H4B4 and ABL-93c developed by J.T. August was obtained from the Developmental Studies Hybridoma Bank, created by the NICHD of the NIH and maintained at the University of Iowa, Department of Biology, Iowa City, IA 52242. We also thank the Microscopy Core Facility, in particular Lydia Maus and Pia Stausberg, of the Medical Faculty at the University of Bonn for providing support and instrumentation funded by the Deutsche Forschungsgemeinschaft, Project Number: 388169927 (Confocal microscope) and 388171357 (Electron microscope).The authors would like to thank T. Bajaj and Dr. N. Gassen (University Clinic Bonn), and Dr. J. Höhfeld (University of Bonn) for sharing GFP-LC3-LC3Δ-RFP and mCherry-GFP-LC3B reporter cDNA constructs, scientific discussions, and result interpretation. The monoclonal antibodies H4B4 and ABL-93c developed by J.T. August was obtained from the Developmental Studies Hybridoma Bank, created by the NICHD of the NIH and maintained at the University of Iowa, Department of Biology, Iowa City, IA 52242. We also thank the Microscopy Core Facility, in particular Lydia Maus and Pia Stausberg, of the Medical Faculty at the University of Bonn for providing support and instrumentation funded by the Deutsche Forschungsgemeinschaft, Project Number: 388169927 (Confocal microscope) and 388171357 (Electron microscope).
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