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

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

Risultato della ricerca: Article

3 Citazioni (Scopus)

Abstract

뱉synuclein 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 뱉synuclein 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 뱉synuclein and two familial mutants, A30P and A53T. Our results enlighten the different reversible nature of 뱉synuclein 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 뱉synuclein 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.
Lingua originaleEnglish
pagine (da-a)46-55
Numero di pagine10
RivistaArchives of Biochemistry and Biophysics
Volume627
Stato di pubblicazionePublished - 2017

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology

Cita questo

Militello, V., Piccirilli, F., Ortore, M. G., Lupi, S., Mariani, P., Amenitsch, H., Piccirilli, F., Baldassarri, E., Plotegher, N., Tessari, I., Perucchi, A., Bubacco, L., Steinhart, M., Beltramini, M., & Spinozzi, F. (2017). Pressure effects on α-synuclein amyloid fibrils: An experimental investigation on their dissociation and reversible nature. Archives of Biochemistry and Biophysics, 627, 46-55.