| Full text | |
| Author(s): Show less - |
Gonzalez-Lizarraga, Florencia
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Socias, Sergio B.
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Avila, Cesar L.
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Torres-Bugeau, Clarisa M.
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Barbosa, Leandro R. S.
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Binolfi, Andres
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Sepulveda-Diaz, Julia E.
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Del-Bel, Elaine
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Fernandez, Claudio O.
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Papy-Garcia, Dulce
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Itri, Rosangela
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Raisman-Vozari, Rita
;
Chehin, Rosana N.
Total Authors: 13
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| Document type: | Journal article |
| Source: | SCIENTIFIC REPORTS; v. 7, FEB 3 2017. |
| Web of Science Citations: | 23 |
| Abstract | |
Synucleinophaties are progressive neurodegenerative disorders with no cure to date. An attractive strategy to tackle this problem is repurposing already tested safe drugs against novel targets. In this way, doxycycline prevents neurodegeneration in Parkinson models by modulating neuroinflammation. However, anti-inflammatory therapy per se is insufficient to account for neuroprotection. Herein we characterise novel targets of doxycycline describing the structural background supporting its effectiveness as a neuroprotector at subantibiotic doses. Our results show that doxycycline reshapes alpha-synuclein oligomers into off-pathway, high-molecular-weight species that do not evolve into fibrils. Off-pathway species present less hydrophobic surface than on-pathway oligomers and display different beta-sheet structural arrangement. These structural changes affect the alpha-synuclein ability to destabilize biological membranes, cell viability, and formation of additional toxic species. Altogether, these mechanisms could act synergically giving novel targets for repurposing this drug. (AU) | |
| FAPESP's process: | 14/50766-2 - Towards understanding the role of oxidized lipid membrane on amyloidogenic diseases: biophysical and structural characterization of membrane-induced GAPDH protofibrils |
| Grantee: | Rosangela Itri |
| Support Opportunities: | Regular Research Grants |