Inhibition of alpha-synuclein seeded fibril formation and toxicity by herbal medicinal extracts
<h3>Background</h3><p dir="ltr">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. T...
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2020
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| _version_ | 1864513512317911040 |
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| author | Mustafa T. Ardah (4858657) |
| author2 | Simona S. Ghanem (12267227) Sara A. Abdulla (13902015) Guohua Lv (703840) Mohamed M. Emara (9913215) Katerina E. Paleologou (18877210) Nishant N. Vaikath (2901785) Jia-Hong Lu (2741131) Min Li (12799) Konstantinos Vekrellis (8548056) David Eliezer (325909) Omar M. A. El-Agnaf (8809331) |
| author2_role | author author author author author author author author author author author |
| author_facet | Mustafa T. Ardah (4858657) Simona S. Ghanem (12267227) Sara A. Abdulla (13902015) Guohua Lv (703840) Mohamed M. Emara (9913215) Katerina E. Paleologou (18877210) Nishant N. Vaikath (2901785) Jia-Hong Lu (2741131) Min Li (12799) Konstantinos Vekrellis (8548056) David Eliezer (325909) Omar M. A. El-Agnaf (8809331) |
| author_role | author |
| dc.creator.none.fl_str_mv | Mustafa T. Ardah (4858657) Simona S. Ghanem (12267227) Sara A. Abdulla (13902015) Guohua Lv (703840) Mohamed M. Emara (9913215) Katerina E. Paleologou (18877210) Nishant N. Vaikath (2901785) Jia-Hong Lu (2741131) Min Li (12799) Konstantinos Vekrellis (8548056) David Eliezer (325909) Omar M. A. El-Agnaf (8809331) |
| dc.date.none.fl_str_mv | 2020-03-06T03:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1186/s12906-020-2849-1 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Inhibition_of_alpha-synuclein_seeded_fibril_formation_and_toxicity_by_herbal_medicinal_extracts/26095093 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biomedical and clinical sciences Neurosciences Pharmacology and pharmaceutical sciences Chemical sciences Medicinal and biomolecular chemistry Health sciences Traditional, complementary and integrative medicine α-Synuclein Parkinson’s disease Seeded fibril formation Amyloid fibrils Salvianolic acid B Dihydromyricetin |
| dc.title.none.fl_str_mv | Inhibition of alpha-synuclein seeded fibril formation and toxicity by herbal medicinal extracts |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <h3>Background</h3><p dir="ltr">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.</p><h3>Methods</h3><p dir="ltr">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.</p><h3>Results</h3><p dir="ltr">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 predominantly to monomers, while dihydromyricetin binds to oligomeric species and to a lower extent to monomers. Remarkably, these two compounds stabilized the soluble non-toxic oligomers lacking β-sheet content after subjecting them to proteinase K digestion.</p><h3>Conclusions</h3><p dir="ltr">Eleven compounds were tested but only two showed inhibition of α-syn aggregation, seeded fibril formation and toxicity in vitro. These findings highlight an essential beginning for development of new molecules in the field of synucleinopathies treatment.</p><h2>Other Information</h2><p dir="ltr">Published in: BMC Complementary Medicine and Therapies<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1186/s12906-020-2849-1" target="_blank">https://dx.doi.org/10.1186/s12906-020-2849-1</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_ce73558a60a2eb34a766cc60924d131c |
| identifier_str_mv | 10.1186/s12906-020-2849-1 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/26095093 |
| publishDate | 2020 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Inhibition of alpha-synuclein seeded fibril formation and toxicity by herbal medicinal extractsMustafa T. Ardah (4858657)Simona S. Ghanem (12267227)Sara A. Abdulla (13902015)Guohua Lv (703840)Mohamed M. Emara (9913215)Katerina E. Paleologou (18877210)Nishant N. Vaikath (2901785)Jia-Hong Lu (2741131)Min Li (12799)Konstantinos Vekrellis (8548056)David Eliezer (325909)Omar M. A. El-Agnaf (8809331)Biomedical and clinical sciencesNeurosciencesPharmacology and pharmaceutical sciencesChemical sciencesMedicinal and biomolecular chemistryHealth sciencesTraditional, complementary and integrative medicineα-SynucleinParkinson’s diseaseSeeded fibril formationAmyloid fibrilsSalvianolic acid BDihydromyricetin<h3>Background</h3><p dir="ltr">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.</p><h3>Methods</h3><p dir="ltr">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.</p><h3>Results</h3><p dir="ltr">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 predominantly to monomers, while dihydromyricetin binds to oligomeric species and to a lower extent to monomers. Remarkably, these two compounds stabilized the soluble non-toxic oligomers lacking β-sheet content after subjecting them to proteinase K digestion.</p><h3>Conclusions</h3><p dir="ltr">Eleven compounds were tested but only two showed inhibition of α-syn aggregation, seeded fibril formation and toxicity in vitro. These findings highlight an essential beginning for development of new molecules in the field of synucleinopathies treatment.</p><h2>Other Information</h2><p dir="ltr">Published in: BMC Complementary Medicine and Therapies<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1186/s12906-020-2849-1" target="_blank">https://dx.doi.org/10.1186/s12906-020-2849-1</a></p>2020-03-06T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1186/s12906-020-2849-1https://figshare.com/articles/journal_contribution/Inhibition_of_alpha-synuclein_seeded_fibril_formation_and_toxicity_by_herbal_medicinal_extracts/26095093CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/260950932020-03-06T03:00:00Z |
| spellingShingle | Inhibition of alpha-synuclein seeded fibril formation and toxicity by herbal medicinal extracts Mustafa T. Ardah (4858657) Biomedical and clinical sciences Neurosciences Pharmacology and pharmaceutical sciences Chemical sciences Medicinal and biomolecular chemistry Health sciences Traditional, complementary and integrative medicine α-Synuclein Parkinson’s disease Seeded fibril formation Amyloid fibrils Salvianolic acid B Dihydromyricetin |
| status_str | publishedVersion |
| title | Inhibition of alpha-synuclein seeded fibril formation and toxicity by herbal medicinal extracts |
| title_full | Inhibition of alpha-synuclein seeded fibril formation and toxicity by herbal medicinal extracts |
| title_fullStr | Inhibition of alpha-synuclein seeded fibril formation and toxicity by herbal medicinal extracts |
| title_full_unstemmed | Inhibition of alpha-synuclein seeded fibril formation and toxicity by herbal medicinal extracts |
| title_short | Inhibition of alpha-synuclein seeded fibril formation and toxicity by herbal medicinal extracts |
| title_sort | Inhibition of alpha-synuclein seeded fibril formation and toxicity by herbal medicinal extracts |
| topic | Biomedical and clinical sciences Neurosciences Pharmacology and pharmaceutical sciences Chemical sciences Medicinal and biomolecular chemistry Health sciences Traditional, complementary and integrative medicine α-Synuclein Parkinson’s disease Seeded fibril formation Amyloid fibrils Salvianolic acid B Dihydromyricetin |