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Chemistry (Weinheim an der Bergstrasse, Germany)

Small-Molecule-Induced Soluble Oligomers of α-Synuclein with Helical Structure.


PMID 28763125

Abstract

Accumulation of α-synuclein (αSyn) aggregates constitutes the hallmark of synucleinopathies including Parkinson's disease. However, many steps from the innocuous, monomeric αSyn toward misfolded oligomers and fibrillar species remain unclear. Here, we show that αSyn can form in solution α-helical oligomers, which are off-pathway to fibrillization, through interaction with the tetrapyrrole phthalocyanine tetrasulfonate. Chemical cross-linking combined with mass spectrometry reveals a large number of intermolecular cross-links along the entire αSyn sequence in the phthalocyanine tetrasulfonate-stabilized αSyn oligomers. Our study suggests that stabilization of structured oligomers by small molecules provides a viable strategy to interfere with αSyn fibrillization.

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P4374
Phthalocyanine tetrasulfonate hydrate, solid
C32H18N8O12S4 · xH2O