Dihydromyricetin and Salvianolic acid B inhibit alpha-synuclein aggregation and enhance chaperone-mediated autophagy
<h3>Background</h3><p dir="ltr">Progressive accumulation of α-synuclein is a key step in the pathological development of Parkinson’s disease. Impaired protein degradation and increased levels of α-synuclein may trigger a pathological aggregation <i>in vitro</i>...
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| مؤلفون آخرون: | , , , , , , , , , |
| منشور في: |
2019
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| _version_ | 1864513514172841984 |
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| author | Jia-Zhen Wu (6844793) |
| author2 | Mustafa Ardah (2134240) Caroline Haikal (5471201) Alexander Svanbergsson (6844796) Meike Diepenbroek (6844799) Nishant N. Vaikath (2901785) Wen Li (143214) Zhan-You Wang (358606) Tiago F. Outeiro (191379) Omar M. El-Agnaf (3172641) Jia-Yi Li (24812) |
| author2_role | author author author author author author author author author author |
| author_facet | Jia-Zhen Wu (6844793) Mustafa Ardah (2134240) Caroline Haikal (5471201) Alexander Svanbergsson (6844796) Meike Diepenbroek (6844799) Nishant N. Vaikath (2901785) Wen Li (143214) Zhan-You Wang (358606) Tiago F. Outeiro (191379) Omar M. El-Agnaf (3172641) Jia-Yi Li (24812) |
| author_role | author |
| dc.creator.none.fl_str_mv | Jia-Zhen Wu (6844793) Mustafa Ardah (2134240) Caroline Haikal (5471201) Alexander Svanbergsson (6844796) Meike Diepenbroek (6844799) Nishant N. Vaikath (2901785) Wen Li (143214) Zhan-You Wang (358606) Tiago F. Outeiro (191379) Omar M. El-Agnaf (3172641) Jia-Yi Li (24812) |
| dc.date.none.fl_str_mv | 2019-06-15T03:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1186/s40035-019-0159-7 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Dihydromyricetin_and_Salvianolic_acid_B_inhibit_alpha-synuclein_aggregation_and_enhance_chaperone-mediated_autophagy/25904005 |
| 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 chaperone-mediated autophagy macroautophagy alpha-synuclein protein aggregation Parkinson disease lysosomal-associated membrane protein |
| dc.title.none.fl_str_mv | Dihydromyricetin and Salvianolic acid B inhibit alpha-synuclein aggregation and enhance chaperone-mediated autophagy |
| 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">Progressive accumulation of α-synuclein is a key step in the pathological development of Parkinson’s disease. Impaired protein degradation and increased levels of α-synuclein may trigger a pathological aggregation <i>in vitro</i> and <i>in vivo</i>. The chaperone-mediated autophagy (CMA) pathway is involved in the intracellular degradation processes of α-synuclein. Dysfunction of the CMA pathway impairs α-synuclein degradation and causes cytotoxicity.</p><h3>Results</h3><p dir="ltr">In the present study, we investigated the effects on the CMA pathway and α-synuclein aggregation using bioactive ingredients (Dihydromyricetin (DHM) and Salvianolic acid B (Sal B)) extracted from natural medicinal plants. In both cell-free and cellular models of α-synuclein aggregation, after administration of DHM and Sal B, we observed significant inhibition of α-synuclein accumulation and aggregation. Cells were co-transfected with a C-terminal modified α-synuclein (SynT) and synphilin-1, and then treated with DHM (10 μM) and Sal B (50 μM) 16 hours after transfection; levels of α-synuclein aggregation decreased significantly (68% for DHM and 75% for Sal B). Concomitantly, we detected increased levels of LAMP-1 (a marker of lysosomal homeostasis) and LAMP-2A (a key marker of CMA). Immunofluorescence analyses showed increased colocalization between LAMP-1 and LAMP-2A with α-synuclein inclusions after treatment with DHM and Sal B. We also found increased levels of LAMP-1 and LAMP-2A both <i>in vitro</i> and <i>in vivo</i>, along with decreased levels of α-synuclein. Moreover, DHM and Sal B treatments exhibited anti-inflammatory activities, preventing astroglia- and microglia-mediated neuroinflammation in BAC-α-syn-GFP transgenic mice.</p><h3>Conclusions</h3><p dir="ltr">Our data indicate that DHM and Sal B are effective in modulating α-synuclein accumulation and aggregate formation and augmenting activation of CMA, holding potential for the treatment of Parkinson’s disease.</p><h2>Other Information</h2><p dir="ltr">Published in: Translational Neurodegeneration<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/s40035-019-0159-7" target="_blank">https://dx.doi.org/10.1186/s40035-019-0159-7</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_c333c263c99fe2bbdf6c32e120ed1600 |
| identifier_str_mv | 10.1186/s40035-019-0159-7 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/25904005 |
| publishDate | 2019 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Dihydromyricetin and Salvianolic acid B inhibit alpha-synuclein aggregation and enhance chaperone-mediated autophagyJia-Zhen Wu (6844793)Mustafa Ardah (2134240)Caroline Haikal (5471201)Alexander Svanbergsson (6844796)Meike Diepenbroek (6844799)Nishant N. Vaikath (2901785)Wen Li (143214)Zhan-You Wang (358606)Tiago F. Outeiro (191379)Omar M. El-Agnaf (3172641)Jia-Yi Li (24812)Biomedical and clinical sciencesNeuroscienceschaperone-mediated autophagymacroautophagyalpha-synucleinprotein aggregationParkinson diseaselysosomal-associated membrane protein<h3>Background</h3><p dir="ltr">Progressive accumulation of α-synuclein is a key step in the pathological development of Parkinson’s disease. Impaired protein degradation and increased levels of α-synuclein may trigger a pathological aggregation <i>in vitro</i> and <i>in vivo</i>. The chaperone-mediated autophagy (CMA) pathway is involved in the intracellular degradation processes of α-synuclein. Dysfunction of the CMA pathway impairs α-synuclein degradation and causes cytotoxicity.</p><h3>Results</h3><p dir="ltr">In the present study, we investigated the effects on the CMA pathway and α-synuclein aggregation using bioactive ingredients (Dihydromyricetin (DHM) and Salvianolic acid B (Sal B)) extracted from natural medicinal plants. In both cell-free and cellular models of α-synuclein aggregation, after administration of DHM and Sal B, we observed significant inhibition of α-synuclein accumulation and aggregation. Cells were co-transfected with a C-terminal modified α-synuclein (SynT) and synphilin-1, and then treated with DHM (10 μM) and Sal B (50 μM) 16 hours after transfection; levels of α-synuclein aggregation decreased significantly (68% for DHM and 75% for Sal B). Concomitantly, we detected increased levels of LAMP-1 (a marker of lysosomal homeostasis) and LAMP-2A (a key marker of CMA). Immunofluorescence analyses showed increased colocalization between LAMP-1 and LAMP-2A with α-synuclein inclusions after treatment with DHM and Sal B. We also found increased levels of LAMP-1 and LAMP-2A both <i>in vitro</i> and <i>in vivo</i>, along with decreased levels of α-synuclein. Moreover, DHM and Sal B treatments exhibited anti-inflammatory activities, preventing astroglia- and microglia-mediated neuroinflammation in BAC-α-syn-GFP transgenic mice.</p><h3>Conclusions</h3><p dir="ltr">Our data indicate that DHM and Sal B are effective in modulating α-synuclein accumulation and aggregate formation and augmenting activation of CMA, holding potential for the treatment of Parkinson’s disease.</p><h2>Other Information</h2><p dir="ltr">Published in: Translational Neurodegeneration<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/s40035-019-0159-7" target="_blank">https://dx.doi.org/10.1186/s40035-019-0159-7</a></p>2019-06-15T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1186/s40035-019-0159-7https://figshare.com/articles/journal_contribution/Dihydromyricetin_and_Salvianolic_acid_B_inhibit_alpha-synuclein_aggregation_and_enhance_chaperone-mediated_autophagy/25904005CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/259040052019-06-15T03:00:00Z |
| spellingShingle | Dihydromyricetin and Salvianolic acid B inhibit alpha-synuclein aggregation and enhance chaperone-mediated autophagy Jia-Zhen Wu (6844793) Biomedical and clinical sciences Neurosciences chaperone-mediated autophagy macroautophagy alpha-synuclein protein aggregation Parkinson disease lysosomal-associated membrane protein |
| status_str | publishedVersion |
| title | Dihydromyricetin and Salvianolic acid B inhibit alpha-synuclein aggregation and enhance chaperone-mediated autophagy |
| title_full | Dihydromyricetin and Salvianolic acid B inhibit alpha-synuclein aggregation and enhance chaperone-mediated autophagy |
| title_fullStr | Dihydromyricetin and Salvianolic acid B inhibit alpha-synuclein aggregation and enhance chaperone-mediated autophagy |
| title_full_unstemmed | Dihydromyricetin and Salvianolic acid B inhibit alpha-synuclein aggregation and enhance chaperone-mediated autophagy |
| title_short | Dihydromyricetin and Salvianolic acid B inhibit alpha-synuclein aggregation and enhance chaperone-mediated autophagy |
| title_sort | Dihydromyricetin and Salvianolic acid B inhibit alpha-synuclein aggregation and enhance chaperone-mediated autophagy |
| topic | Biomedical and clinical sciences Neurosciences chaperone-mediated autophagy macroautophagy alpha-synuclein protein aggregation Parkinson disease lysosomal-associated membrane protein |