Inhibition of alpha-synuclein seeded fibril formation and toxicity by herbal medicinal extracts

BMC Complementary Medicine and Therapies
Mustafa T ArdahOmar M A El-Agnaf

Abstract

Recent studies indicated that seeded fibril formation and toxicity of α-synuclein (α-syn) play a main role in the pathogenesis of certain diseases including Parkinson's disease (PD), multiple system atrophy, and dementia with Lewy bodies. Therefore, examination of compounds that abolish the process of seeding is considered a key step towards therapy of several synucleinopathies. Using biophysical, biochemical and cell-culture-based assays, assessment of eleven compounds, extracted from Chinese medicinal herbs, was performed in this study for their effect on α-syn fibril formation and toxicity caused by the seeding process. Salvianolic acid B and dihydromyricetin were the two compounds that strongly inhibited the fibril growth and neurotoxicity of α-syn. In an in-vitro cell model, these compounds decreased the insoluble phosphorylated α-syn and aggregation. Also, in primary neuronal cells, these compounds showed a reduction in α-syn aggregates. Both compounds inhibited the seeded fibril growth with dihydromyricetin having the ability to disaggregate preformed α-syn fibrils. In order to investigate the inhibitory mechanisms of these two compounds towards fibril formation, we demonstrated that salvianolic acid B binds predominantl...Continue Reading

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Citations

Jan 12, 2021·The Journal of Membrane Biology·Daniel E OtzenFarhang Aliakbari
May 16, 2021·International Journal of Biological Macromolecules·Ankita R RaneSinjan Choudhary
Jul 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Simona S GhanemOmar M A El-Agnaf
Aug 7, 2021·Saudi Journal of Biological Sciences·Dong WangSeyyed Shamsadin Athari
Oct 24, 2021·Journal of Neurochemistry·Maksym GalkinVolodymyr V Shvadchak

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Methods Mentioned

BETA
protein assay
electron microscopy
gel filtration
NMR
transfection

Software Mentioned

GraphPad
imageJ

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Alpha-Synuclein Aggregation (MDS)

Alpha-synucleins are small proteins that are believed to restrict the mobility of synpatic vesicles and inhibit neurotransmitter release. Aggregation of these proteins have been linked to several types of neurodegenerative diseases including dementia with Lewy bodies and Parkinson's disease. Here is the latest research on α-synuclein aggregation.

Alpha-Synuclein Aggregation

Alpha-synucleins are small proteins that are believed to restrict the mobility of synpatic vesicles and inhibit neurotransmitter release. Aggregation of these proteins have been linked to several types of neurodegenerative diseases including dementia with Lewy bodies and Parkinson's disease. Here is the latest research on α-synuclein aggregation.

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