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Updated: Apr 19, 2026

Fractionation for Resolution of Soluble and Insoluble Huntingtin Species
Published on: February 27, 2018
Small molecule-mediated stabilization of vesicle-associated helical α-synuclein inhibits pathogenic misfolding and
Luis Fonseca-Ornelas1, Sybille E Eisbach2, Maria Paulat1
1Department for NMR-based Structural Biology, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany.
Abstract:
α-synuclein is an abundant presynaptic protein that is important for regulation of synaptic vesicle trafficking, and whose misfolding plays a key role in Parkinson's disease. While α-synuclein is disordered in solution, it folds into a helical conformation when bound to synaptic vesicles. Stabilization of helical, folded α-synuclein might therefore interfere with α-synuclein-induced neurotoxicity. Here we show that several small molecules, which delay aggregation of α-synuclein in solution, including the Parkinson's disease drug selegiline, fail to interfere with misfolding of vesicle-bound α-synuclein. In contrast, the porphyrin phtalocyanine tetrasulfonate directly binds to vesicle-bound α-synuclein, stabilizes its helical conformation and thereby delays pathogenic misfolding and aggregation. Our study suggests that small-molecule-mediated stabilization of helical vesicle-bound α-synuclein opens new possibilities to target Parkinson's disease and related synucleinopathies.
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