Nanoscopic Characterisation of Individual Endogenous Protein Aggregates in Human Neuronal Cells

Abstract: 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.

Standort
Deutsche Nationalbibliothek Frankfurt am Main
Umfang
Online-Ressource
Sprache
Englisch

Erschienen in
Nanoscopic Characterisation of Individual Endogenous Protein Aggregates in Human Neuronal Cells ; volume:19 ; number:19 ; year:2018 ; pages:2033-2038 ; extent:6
ChemBioChem ; 19, Heft 19 (2018), 2033-2038 (gesamt 6)

Urheber
Whiten, Daniel R.
Zuo, Yukun
Calo, Laura
Choi, Minee‐Liane
De, Suman
Flagmeier, Patrick
Wirthensohn, David C.
Kundel, Franziska
Ranasinghe, Rohan T.
Sanchez, Santiago E.
Athauda, Dilan
Lee, Steven F.
Dobson, Christopher M.
Gandhi, Sonia
Spillantini, Maria‐Grazia
Klenerman, David
Horrocks, Mathew H.

DOI
10.1002/cbic.201800209
URN
urn:nbn:de:101:1-2022081509391370557716
Rechteinformation
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Letzte Aktualisierung
15.08.2025, 07:35 MESZ

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Beteiligte

  • Whiten, Daniel R.
  • Zuo, Yukun
  • Calo, Laura
  • Choi, Minee‐Liane
  • De, Suman
  • Flagmeier, Patrick
  • Wirthensohn, David C.
  • Kundel, Franziska
  • Ranasinghe, Rohan T.
  • Sanchez, Santiago E.
  • Athauda, Dilan
  • Lee, Steven F.
  • Dobson, Christopher M.
  • Gandhi, Sonia
  • Spillantini, Maria‐Grazia
  • Klenerman, David
  • Horrocks, Mathew H.

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