4.7 Article

Evidence of the existence of micellar-like aggregates for ?-synuclein

Journal

INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
Volume 177, Issue -, Pages 392-400

Publisher

ELSEVIER
DOI: 10.1016/j.ijbiomac.2021.02.150

Keywords

-Synuclein; Light scattering; Micellar-like aggregates

Funding

  1. National Foundation for Science and Technology (FCT) [PEstOE/QUI/UI0100/2011, SFRH/BPD/37016/2007]

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The investigation focused on early Syn aggregates revealed that the micellar-like aggregates formed at around 10 μM and evolved into smaller aggregates (possibly oligomers) at higher protein concentrations. These active species seem to play a role in the protein aggregation mechanism.
We have been investigating the early stages of alpha-synuclein (Syn) aggregation, a small presynaptic protein implicated in Parkinson's disease. We previously reported that for pH jumps (1000 s) from pH 7 to pH 2 the variation of the Syn intrinsic fluorescence intensity did not change in the concentration range of ca. 10-50 mu M (ref. 16). Additionally, I reported dynamic light scattering (DLS) experiments revealing the formation of early large Syn aggregates (ref. 7). These reported results mean that some molecular entity is being early formed. Herein, it was decided to investigate in detail these early Syn aggregates by using light scattering. By DLS analysis, these aggregates exhibited a hydrodynamic diameter of ca. 420 nm along with a high scattering intensity, characteristic of micellar-like aggregates formation. The critical micelle concentration (CMC) at which the Syn micellar-like aggregates are formed was ca. 10 mu M. DLS analysis has also revealed that the micellar-like aggregates for Syn evolved, for protein concentrations >100 mu M, to the formation of smaller aggregates (hydrodynamic diameter of ca. 165 nm), possibly Syn oligomers. The Syn micellar-like aggregates formed at pH 7 solutions seem to be active species and to have a role in this protein aggregation mechanism. (c) 2021 Elsevier B.V. All rights reserved.

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