TY - JOUR
T1 - Pressure effects on α-synuclein amyloid fibrils
T2 - An experimental investigation on their dissociation and reversible nature
AU - Piccirilli, Federica
AU - Plotegher, Nicoletta
AU - Spinozzi, Francesco
AU - Bubacco, Luigi
AU - Mariani, Paolo
AU - Beltramini, Mariano
AU - Tessari, Isabella
AU - Militello, Valeria
AU - Perucchi, Andrea
AU - Amenitsch, Heinz
AU - Baldassarri, Enrico
AU - Steinhart, Milos
AU - Lupi, Stefano
AU - Ortore, Maria Grazia
PY - 2017/8/1
Y1 - 2017/8/1
N2 - 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.
AB - 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.
KW - Amyloid
KW - FTIR
KW - High-pressure
KW - SAXS
KW - α-synuclein
UR - http://www.scopus.com/inward/record.url?scp=85021295243&partnerID=8YFLogxK
U2 - 10.1016/j.abb.2017.06.007
DO - 10.1016/j.abb.2017.06.007
M3 - Article
C2 - 28624352
AN - SCOPUS:85021295243
SN - 0003-9861
VL - 627
SP - 46
EP - 55
JO - Archives of Biochemistry and Biophysics
JF - Archives of Biochemistry and Biophysics
ER -