Title | The neurotransmitter serotonin interrupts α-synuclein amyloid maturation. |
Publication Type | Journal Article |
Year of Publication | 2011 |
Authors | S Falsone, F., G. Leitinger, A. Karner, A. J. Kungl, S. Kosol, R. Cappai, and K. Zangger |
Journal | Biochim Biophys Acta |
Volume | 1814 |
Issue | 5 |
Pagination | 553-61 |
Date Published | 2011 May |
ISSN | 0006-3002 |
Keywords | alpha-Synuclein, Amyloid, Circular Dichroism, Electrophoresis, Polyacrylamide Gel, Humans, Magnetic Resonance Spectroscopy, Microscopy, Electron, Transmission, Neurotransmitter Agents, Protein Binding, Serotonin |
Abstract | Indolic derivatives can affect fibril growth of amyloid forming proteins. The neurotransmitter serotonin (5-HT) is of particular interest, as it is an endogenous molecule with a possible link to neuropsychiatric symptoms of Parkinson disease. A key pathomolecular mechanism of Parkinson disease is the misfolding and aggregation of the intrinsically unstructured protein α-synuclein. We performed a biophysical study to investigate an influence between these two molecules. In an isolated in vitro system, 5-HT interfered with α-synuclein amyloid fiber maturation, resulting in the formation of partially structured, SDS-resistant intermediate aggregates. The C-terminal region of α-synuclein was essential for this interaction, which was driven mainly by electrostatic forces. 5-HT did not bind directly to monomeric α-synuclein molecules and we propose a model where 5-HT interacts with early intermediates of α-synuclein amyloidogenesis, which disfavors their further conversion into amyloid fibrils. |
DOI | 10.1016/j.bbapap.2011.02.008 |
Alternate Journal | Biochim. Biophys. Acta |
PubMed ID | 21376144 |
PubMed Central ID | PMC3092864 |
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