Hyperosmotic stress induces cell-dependent aggregation of α-synuclein

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  • Alexandra M.C. Fragniere, University of Cambridge, School of Clinical Medicine
  • ,
  • Simon R.W. Stott, University of Cambridge, School of Clinical Medicine
  • ,
  • Shaline V. Fazal, University of Cambridge, School of Clinical Medicine
  • ,
  • Maria Andreasen
  • Kirsten Scott, University of Cambridge, School of Clinical Medicine
  • ,
  • Roger A. Barker, University of Cambridge, School of Clinical Medicine, Wellcome Trust-MRC Stem Cell Institute

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.

Original languageEnglish
Article number2288
JournalScientific Reports
Volume9
Number of pages11
ISSN2045-2322
DOIs
Publication statusPublished - Dec 2019

    Research areas

  • DISEASE, DYNAMICS, FIBRILS, FILAMENTS, KEY ROLE, MUTANT, PRION, PROTEIN AGGREGATION, SECONDARY STRUCTURE, WATER

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