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Vitamins K interact with N-terminus α-synuclein and modulate the protein fibrillization in vitro. Exploring the interaction between quinones and α-synuclein.
- Source :
-
Neurochemistry international [Neurochem Int] 2013 Jan; Vol. 62 (1), pp. 103-12. Date of Electronic Publication: 2012 Oct 12. - Publication Year :
- 2013
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Abstract
- In the last decades, a series of compounds, including quinones and polyphenols, has been described as having anti-fibrillogenic action on α-synuclein (α-syn) whose aggregation is associated to the pathogenesis of Parkinson's disease (PD). Most of these molecules act as promiscuous anti-amyloidogenic agents, interacting with the diverse amyloidogenic proteins (mostly unfolded) through non-specific hydrophobic interactions. Herein we investigated the effect of the vitamins K (phylloquinone, menaquinone and menadione), which are 1,4-naphthoquinone (1,4-NQ) derivatives, on α-syn aggregation, comparing them with other anti-fibrillogenic molecules such as quinones, polyphenols and lipophilic vitamins. Vitamins K delayed α-syn fibrillization in substoichiometric concentrations, leading to the formation of short, sheared fibrils and amorphous aggregates, which are less prone to produce leakage of synthetic vesicles. In seeding conditions, menadione and 1,4-NQ significantly inhibited fibrils elongation, which could be explained by their ability to destabilize preformed fibrils of α-syn. Bidimensional NMR experiments indicate that a specific site at the N-terminal α-syn (Gly31/Lys32) is involved in the interaction with vitamins K, which is corroborated by previous studies suggesting that Lys is a key residue in the interaction with quinones. Together, our data suggest that 1,4-NQ, recently showed up by our group as a potential scaffold for designing new monoamine oxidase inhibitors, is also capable to modulate α-syn fibrillization in vitro.<br /> (Copyright © 2012 Elsevier Ltd. All rights reserved.)
- Subjects :
- Cell Nucleus drug effects
Humans
Magnetic Resonance Spectroscopy
Microscopy, Atomic Force
Naphthoquinones pharmacology
Vitamin K analogs & derivatives
Vitamin K chemistry
Vitamin K 1 pharmacology
Vitamin K 2 pharmacology
Vitamin K 3 pharmacology
alpha-Synuclein genetics
Antifibrinolytic Agents
Neurofibrils drug effects
Quinones pharmacology
Vitamin K pharmacology
alpha-Synuclein metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1872-9754
- Volume :
- 62
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Neurochemistry international
- Publication Type :
- Academic Journal
- Accession number :
- 23064431
- Full Text :
- https://doi.org/10.1016/j.neuint.2012.10.001