Piccirilli, F;
Plotegher, N;
Spinozzi, F;
Bubacco, L;
Mariani, P;
Beltramini, M;
Tessari, I;
... Ortore, MG; + view all
(2017)
Pressure effects on α-synuclein amyloid fibrils: An experimental investigation on their dissociation and reversible nature.
Archives of Biochemistry and Biophysics
, 627
pp. 46-55.
10.1016/j.abb.2017.06.007.
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Abstract
α-synuclein amyloid fibrils are found in surviving neurons of Parkinson's disease affected patients, but the role they play in the disease development is still under debate. A growing number of evidences points to soluble oligomers as the major cytotoxic species, while insoluble fibrillar aggregates could even play a protection role. In this work, we investigate α-synuclein fibrils dissociation induced at high pressure by means of Small Angle X-ray Scattering and Fourier Transform Infrared Spectroscopy. Fibrils were produced from wild type α-synuclein and two familial mutants, A30P and A53T. Our results enlighten the different reversible nature of α-synuclein fibrils fragmentation at high pressure and suggest water excluded volumes presence in the fibrils core. Wild type and A30P species stabilized at high pressure are highly amyloidogenic and quickly re-associate into fibrils upon decompression, while A53T species shows a partial reversibility of the process likely due to the presence of an intermediate oligomeric state stabilized at high pressure. The amyloid fibrils dissociation process is here suggested to be associated to a negative activation volume, supporting the notion that α-synuclein fibrils are in a high-volume and high-compressibility state and hinting at the presence of a hydration-mediated activated state from which dissociation occurs.
| Type: | Article |
|---|---|
| Title: | Pressure effects on α-synuclein amyloid fibrils: An experimental investigation on their dissociation and reversible nature |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.abb.2017.06.007 |
| Publisher version: | http://doi.org/10.1016/j.abb.2017.06.007 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Amyloid, FTIR, High-pressure, SAXS, α-synuclein |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1561554 |
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