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Single-molecule studies of amyloid proteins: from biophysical properties to diagnostic perspectives.
Journal article

Single-molecule studies of amyloid proteins: from biophysical properties to diagnostic perspectives.

  • Wu J Department of Biology and Chemistry, Paul Scherrer Institute, 5232, Villigen, Switzerland.
  • Cao C Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015, Lausanne, Switzerland.
  • Loch RA Department of Biology and Chemistry, Paul Scherrer Institute, 5232, Villigen, Switzerland.
  • Tiiman A Department of Clinical Neuroscience (CNS), Center for Molecular Medicine CMM L8:01, Karolinska Institutet, 17176, Stockholm, Sweden.
  • Luo J Department of Biology and Chemistry, Paul Scherrer Institute, 5232, Villigen, Switzerland.
  • 2020-11-05
Published in:
  • Quarterly reviews of biophysics. - 2020
Amyloid protein
neurodegenerative diseases
single-molecule fluorescence imaging
single-molecule force spectroscopy
single-molecule techniques
single-nanopore electrical recording
English In neurodegenerative diseases, a wide range of amyloid proteins or peptides such as amyloid-beta and α-synuclein fail to keep native functional conformations, followed by misfolding and self-assembling into a diverse array of aggregates. The aggregates further exert toxicity leading to the dysfunction, degeneration and loss of cells in the affected organs. Due to the disordered structure of the amyloid proteins, endogenous molecules, such as lipids, are prone to interact with amyloid proteins at a low concentration and influence amyloid cytotoxicity. The heterogeneity of amyloid proteinscomplicates the understanding of the amyloid cytotoxicity when relying only on conventional bulk and ensemble techniques. As complementary tools, single-molecule techniques (SMTs) provide novel insights into the different subpopulations of a heterogeneous amyloid mixture as well as the cytotoxicity, in particular as involved in lipid membranes. This review focuses on the recent advances of a series of SMTs, including single-molecule fluorescence imaging, single-molecule force spectroscopy and single-nanopore electrical recording, for the understanding of the amyloid molecular mechanism. The working principles, benefits and limitations of each technique are discussed and compared in amyloid protein related studies.. We also discuss why SMTs show great potential and are worthy of further investigation with feasibility studies as diagnostic tools of neurodegenerative diseases and which limitations are to be addressed.
Language
  • English
Open access status
closed
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Persistent URL
https://sonar.ch/global/documents/25410
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