Pressure effects on α-synuclein amyloid fibrils: An experimental investigation on their dissociation and reversible nature

Federica Piccirilli*, Nicoletta Plotegher, Francesco Spinozzi, Luigi Bubacco, Paolo Mariani, Mariano Beltramini, Isabella Tessari, Valeria Militello, Andrea Perucchi, Heinz Amenitsch, Enrico Baldassarri, Milos Steinhart, Stefano Lupi, Maria Grazia Ortore

*Korrespondierende/r Autor/in für diese Arbeit

Publikation: Beitrag in einer FachzeitschriftArtikel


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.

Seiten (von - bis)46-55
FachzeitschriftArchives of Biochemistry and Biophysics
PublikationsstatusVeröffentlicht - 1 Aug 2017

ASJC Scopus subject areas

  • !!Biophysics
  • !!Biochemistry
  • !!Molecular Biology

Fields of Expertise

  • Human- & Biotechnology


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