The neurotransmitter serotonin interrupts α-synuclein amyloid maturation.

TitleThe neurotransmitter serotonin interrupts α-synuclein amyloid maturation.
Publication TypeJournal Article
Year of Publication2011
AuthorsS Falsone, F., G. Leitinger, A. Karner, A. J. Kungl, S. Kosol, R. Cappai, and K. Zangger
JournalBiochim Biophys Acta
Volume1814
Issue5
Pagination553-61
Date Published2011 May
ISSN0006-3002
Keywordsalpha-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.

DOI10.1016/j.bbapap.2011.02.008
Alternate JournalBiochim. Biophys. Acta
PubMed ID21376144
PubMed Central IDPMC3092864