Seed-dependent accelerated fibrillation of alpha-synuclein induced by periodic ultrasonication treatment.
alpha-Synuclein is the major component of Lewy bodies and responsible for the amyloid deposits observed in Parkinson's disease. Ordered filamentous aggregate formation of the natively unfolded a-synuclein was investigated in vitro with the periodic ultrasonication. The ultrasonication induced the fibrillation of a-synuclein, as the random structure gradually converted into a beta-sheet structure. The resulting fibrils obtained at the stationary phase appeared heterogeneous in their size distribution, with the average length and height of 0.28 Mm+/-0.21 Mm and 5.6 nm+/-1.9 nm, respectively. After additional extensive ultrasonication in the absence of monomeric a-synuclein, the equilibrium between the fibril formation and its breakdown shifted to the disintegration of the preexisting fibrils. The resulting fragments served as nucleation centers for the subsequent seed-dependent accelerated fibrillation under a quiescent incubation condition. This self-seeding amplification process depended on the seed formation and subsequent alterations in their properties by the ultrasonication to a state that accretes the monomeric soluble protein more effectively than their reassociation of the seeds back to the original fibrils. Since many neurodegenerative disorders have been considered to be propagated via the seed-dependent amyloidosis, this study would provide a novel aspect of the significance of the seed structure and its properties leading to the accelerated amyloid formation.
Kim
Hyun Jin
HJ
School of Chemical and Biological Engineering, College of Engineering, Seoul National University, Seoul 151-744, Korea.
Chatani
Eri
E
Goto
Yuji
Y
Paik
Seung R
SR
D002942:Circular Dichroism; D007700:Kinetics; D016631:Lewy Bodies / Q000737:chemistry / Q000378:metabolism*; D018625:Microscopy, Atomic Force; D017510:Protein Folding; D017433:Protein Structure, Secondary; D014465:Ultrasonics; D051844:alpha-Synuclein / Q000737:chemistry / Q000378:metabolism*
D051844:alpha-Synuclein