Nanoscopic Characterisation of Individual Endogenous Protein Aggregates in Human Neuronal Cells.

Autor:	Whiten DR; Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK., Zuo Y; Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK., Calo L; Department of Clinical Neurosciences, University of Cambridge, Hills Road, Cambridge, CB2 0AH, UK., Choi ML; UCL Institute of Neurology, Queen Square, London, WC1N 3BG, 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., Kundel F; Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK., Ranasinghe RT; Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK., Sanchez SE; Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK., Athauda D; UCL Institute of Neurology, Queen Square, London, WC1N 3BG, UK., Lee SF; Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK., Dobson CM; Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK., Gandhi S; UCL Institute of Neurology, Queen Square, London, WC1N 3BG, UK., Spillantini MG; Department of Clinical Neurosciences, University of Cambridge, Hills Road, Cambridge, CB2 0AH, 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., Horrocks MH; Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK.; Present addresses: EaStCHEM School of Chemistry, University of Edinburgh, David Brewster Road, Edinburgh, EH9 3FJ, UK.; UK Dementia Research Institute, University of Edinburgh, Edinburgh, UK.
Jazyk:	angličtina
Zdroj:	Chembiochem : a European journal of chemical biology [Chembiochem] 2018 Oct 04; Vol. 19 (19), pp. 2033-2038. Date of Electronic Publication: 2018 Sep 11.
DOI:	10.1002/cbic.201800209
Abstrakt:	The aberrant misfolding and subsequent conversion of monomeric protein into amyloid aggregates characterises many neurodegenerative disorders, including Parkinson's and Alzheimer's diseases. These aggregates are highly heterogeneous in structure, generally of low abundance and typically smaller than the diffraction limit of light (≈250 nm). To overcome the challenges these characteristics pose to the study of endogenous aggregates formed in cells, we have developed a method to characterise them at the nanometre scale without the need for a conjugated fluorophore. Using a combination of DNA PAINT and an amyloid-specific aptamer, we demonstrate that this technique is able to detect and super-resolve a range of aggregated species, including those formed by α-synuclein and amyloid-β. Additionally, this method enables endogenous protein aggregates within cells to be characterised. We found that neuronal cells derived from patients with Parkinson's disease contain a larger number of protein aggregates than those from healthy controls. (© 2018 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)
Databáze:	MEDLINE
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