Inhibiting the Ca 2+ Influx Induced by Human CSF.

Autor:	Drews A; Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK., De S; Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK., Flagmeier P; Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK., Wirthensohn DC; Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK., Chen WH; Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK., Whiten DR; Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK., Rodrigues M; Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK., Vincke C; Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium., Muyldermans S; Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium., Paterson RW; Dementia Research Centre, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK., Slattery CF; Dementia Research Centre, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK., Fox NC; Dementia Research Centre, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK., Schott JM; Dementia Research Centre, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK., Zetterberg H; Clinical Neurochemistry Laboratory, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden; Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK., Dobson CM; Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK., Gandhi S; Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK., Klenerman D; Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK; UK Dementia Research Institute, University of Cambridge, Cambridge CB2 0XY, UK. Electronic address: dk10012@cam.ac.uk.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2017 Dec 12; Vol. 21 (11), pp. 3310-3316.
DOI:	10.1016/j.celrep.2017.11.057
Abstrakt:	One potential therapeutic strategy for Alzheimer's disease (AD) is to use antibodies that bind to small soluble protein aggregates to reduce their toxic effects. However, these therapies are rarely tested in human CSF before clinical trials because of the lack of sensitive methods that enable the measurement of aggregate-induced toxicity at low concentrations. We have developed highly sensitive single vesicle and single-cell-based assays that detect the Ca 2+ influx caused by the CSF of individuals affected with AD and healthy controls, and we have found comparable effects for both types of samples. We also show that an extracellular chaperone clusterin; a nanobody specific to the amyloid-β peptide (Aβ); and bapineuzumab, a humanized monoclonal antibody raised against Aβ, could all reduce the Ca 2+ influx caused by synthetic Aβ oligomers but are less effective in CSF. These assays could be used to characterize potential therapeutic agents in CSF before clinical trials. (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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