Imaging individual protein aggregates to follow aggregation and determine the role of aggregates in neurodegenerative disease.
Biochimica et biophysica acta. Proteins and proteomics
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De, S., & Klenerman, D. (2019). Imaging individual protein aggregates to follow aggregation and determine the role of aggregates in neurodegenerative disease.. Biochimica et biophysica acta. Proteins and proteomics, 1867 (10), 870-878. https://doi.org/10.1016/j.bbapap.2018.12.010
Protein aggregates play a key role in the initiation and spreading of neurodegenerative disease but have been difficult to study due to their low abundance and heterogeneity, in both size and structure. Fluorescence based methods capable of detecting and characterising single aggregates have recently been developed and can be used to measure many important aggregate properties, and can be combined with sensitive assays to measure aggregate toxicity. Here we review these methods and discuss recent examples of their application to determine the molecular mechanism of aggregation and the detection of aggregates in cells and cerebral spinal fluid. The further development of these methods and their application to the aggregates present in humans has the potential to solve a major problem in the field and allow the identification of the key toxic species that should be targeted in therapies.
Animals, Humans, Neurodegenerative Diseases, Molecular Imaging, Optical Imaging, Protein Aggregates
ECH2020 EUROPEAN RESEARCH COUNCIL (ERC) (669237)
External DOI: https://doi.org/10.1016/j.bbapap.2018.12.010
This record's URL: https://www.repository.cam.ac.uk/handle/1810/288682
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/