Differential inhibition of α-synuclein oligomeric and fibrillar assembly in parkinson's disease model by cinnamon extract

Biochimica Et Biophysica Acta
Ronit Shaltiel-KaryoEhud Gazit

Abstract

The oligomeriztion of α-synuclein (α-syn) into ordered assemblies is associated with the symptoms of Parkinson's Disease (PD). Yet, it is still debatable whether oligomers are formed as part of a multistep process towards amyloid fibril formation or alternatively as "off-pathway" aggregates. 100μM α-syn was incubated with decreasing amounts of cinnamon extract precipitation (CEppt). The fibril formation was measured using spectroscopy and microscopy analyses and oligomers were detected using western blot analysis. The secondary structure of the protein was analyzed using CD. Drosophila brains were studied using immunostaining and confocal microscopy. Here we probed the inhibition pattern of oligomeric and fibrillar forms of α-syn, using a natural substance, CEppt which was previously shown to effectively inhibit aggregation of β-amyloid polypeptide. We demonstrated that CEppt has a differential inhibitory effect on the formation of soluble and insoluble aggregates of α-synuclein in vitro. This inhibition pattern revokes the possibility of redirection to "off-pathway" oligomers. When administering to Drosophila fly model expressing mutant A53T α-syn in the nervous system, a significant curative effect on the behavioral symptoms ...Continue Reading

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Citations

May 3, 2014·Evidence-based Complementary and Alternative Medicine : ECAM·Soojin LeeKyoung Sang Cho
Mar 20, 2015·Neural Regeneration Research·Priyanka Pahan, Kalipada Pahan
Jun 15, 2014·Clinical Autonomic Research : Official Journal of the Clinical Autonomic Research Society·Jose-Alberto Palma, Horacio Kaufmann
Oct 7, 2014·Movement Disorders : Official Journal of the Movement Disorder Society·Sheila M Fleming, Alberto J Espay
Jan 27, 2018·Journal of Translational Medicine·Ajaikumar B KunnumakkaraBharat B Aggarwal
Oct 28, 2015·Nature Reviews. Neurology·Lisa Klingelhoefer, Heinz Reichmann
Sep 10, 2020·Journal of Molecular Neuroscience : MN·Doaa QubtyChaim G Pick
Apr 4, 2019·Frontiers in Pharmacology·Hayate JavedShreesh Kumar Ojha
Oct 6, 2020·Frontiers in Cell and Developmental Biology·Maria FoukaMaria Xilouri

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