Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Falsone, SF; Leitinger, G; Karner, A; Kungl, AJ; Kosol, S; Cappai, R; Zangger, K.
The neurotransmitter serotonin interrupts α-synuclein amyloid maturation.
Biochim Biophys Acta. 2011; 1814(5):553-561
Doi: 10.1016/j.bbapap.2011.02.008
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- Führende Autor*innen der Med Uni Graz
- Falsone Salvatore Fabio
- Co-Autor*innen der Med Uni Graz
- Leitinger Gerd
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- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Amyloid - chemistry
- Circular Dichroism -
- Electrophoresis, Polyacrylamide Gel -
- Humans -
- Magnetic Resonance Spectroscopy -
- Microscopy, Electron, Transmission -
- Neurotransmitter Agents - pharmacology
- Protein Binding - drug effects
- Serotonin - pharmacology
- alpha-Synuclein - chemistry
- Find related publications in this database (Keywords)
- Protein misfolding
- Amyloid
- Aggregation
- Parkinson disease
- Neurodegeneration
- Indoleamine