Hyperosmotic stress induces cell-dependent aggregation of α-synuclein.
Fragniere, Alexandra MC
Barker, Roger A
Springer Science and Business Media LLC
MetadataShow full item record
Fragniere, A. M., Stott, S. R., Fazal, S. V., Andreasen, M., Scott, K., & Barker, R. A. (2019). Hyperosmotic stress induces cell-dependent aggregation of α-synuclein.. Sci Rep, 9 (1), 2288. https://doi.org/10.1038/s41598-018-38296-7
The aggregation of alpha-synuclein (α-syn) is a pathological feature of a number of neurodegenerative conditions, including Parkinson's disease. Genetic mutations, abnormal protein synthesis, environmental stress, and aging have all been implicated as causative factors in this process. The importance of water in the polymerisation of monomers, however, has largely been overlooked. In the present study, we highlight the role of hyperosmotic stress in inducing human α-syn to aggregate in cells in vitro, through rapid treatment of the cells with three different osmolytes: sugar, salt and alcohol. This effect is cell-dependent and not due to direct protein-osmolyte interaction, and is specific for α-syn when compared to other neurodegeneration-related proteins, such as Tau or Huntingtin. This new property of α-syn not only highlights a unique aspect of its behaviour which may have some relevance for disease states, but may also be useful as a screening test for compounds to inhibit the aggregation of α-syn in vitro.
Animals, Benzothiazoles, Blotting, Western, Cell Death, Cell Line, Cell Survival, Electrophoresis, Polyacrylamide Gel, HEK293 Cells, Hot Temperature, Humans, Hydrogen Peroxide, L-Lactate Dehydrogenase, Mice, Osmolar Concentration, Parkinson Disease, Sodium Chloride, Sodium Dodecyl Sulfate, Urea, alpha-Synuclein
Funding was by the DDPDgenes, Rosetree Trust, Wellcome Trust PhD Program for Clinicians, the Danish Council for Independent Research | Natural Sciences (FNU-11-113326), the Stem Cell Institute and Wellcome Trust-MRC funded Cambridge Stem Cell Institute and an NIHR award of a Biomedical Research Centre for Addenbrooke’s Hospital/University of Cambridge. RA Barker is an NIHR Senior Investigator.
European Commission FP7 Collaborative projects (CP) (278871)
Cambridge University Hospitals NHS Foundation Trust (CUH) (146281)
Department of Health (via National Institute for Health Research (NIHR)) (NF-SI-0616-10011)
Cambridge University Hospitals NHS Foundation Trust (CUH) (BRC 2012-2017)
Medical Research Council (MC_PC_12009)
Embargo Lift Date
External DOI: https://doi.org/10.1038/s41598-018-38296-7
This record's URL: https://www.repository.cam.ac.uk/handle/1810/288180
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