Rosmarinic acid turned α-syn oligomers into non-toxic species preserving microtubules in Raw 264.7 cells

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dc.article.number107669
dc.article.number107669
dc.catalogadorgjm
dc.contributor.authorFlores, Nicolás
dc.contributor.authorRivillas-Acevedo, Lina
dc.contributor.authorCaballero, Julio
dc.contributor.authorMelo, Francisco
dc.contributor.authorCaballero, Leonardo
dc.contributor.authorAreche, Carlos
dc.contributor.authorFuentealba Patiño, Denis Alberto
dc.contributor.authorAguilar, Felipe
dc.contributor.authorCornejo, Alberto
dc.date.accessioned2025-03-20T13:26:08Z
dc.date.available2025-03-20T13:26:08Z
dc.date.issued2024
dc.description.abstractParkinson's disease (PD) is the second most prevalent neurodegenerative disorder worldwide, and the therapeutic is focused on several approaches including the inhibition of fibril formation by small compounds, avoiding the formation of cytotoxic oligomers. Thus, we decided to explore the capacity of compounds carrying catechol moieties to inhibit the progression of α-synuclein. Overall, the compounds rosmarinic acid (1), carnosic acid (2), carnosol (3), epiisorosmanol (4), and rosmanol (5) avoid the progression of fibril formation assessed by Thiofavine T (ThT), and atomic force microscopy images showed that morphology is influenced for the actions of compounds over fibrillization. Moreover, ITC experiments showed a Kd varying from 28 to 51 µM, the ΔG showed that the reaction between compounds and α-syn is spontaneous, and ΔH is associated with an exothermic reaction, suggesting the interactions of hydrogen bonds among compounds and α-syn. Docking experiments reinforce this idea showing the intermolecular interactions are mostly hydrogen bonding within the sites 2, 9, and 3/13 of α-synuclein, and compounds 1 and 5. Thus, compound 1, rosmarinic acid, interestingly interacts better with site 9 through catechol and Lysines. In cultured Raw 264. 7 cells, the presence of compounds showed that most of them can promote cell differentiation, especially rosmarinic acid, and rosmanol, both preserving tubulin cytoskeleton. However, once we evaluated whether or not the aggregates pre-treated with compounds could prevent the disruption of microtubules of Raw 264.7 cells, only pre-treated aggregates with rosmarinic acid prevented the disruption of the cytoskeleton. Altogether, we showed that especially rosmarinic acid not only inhibits α-syn but stabilizes the remaining aggregates turning them into not-toxic to Raw 264.7 cells suggesting a main role in cell survival and antigen processing in response to external α-syn aggregates.
dc.description.funderFONDECYT
dc.description.funderFondequip
dc.format.extent8 páginas
dc.fuente.origenSCOPUS
dc.identifier.doi10.1016/j.bioorg.2024.107669
dc.identifier.issn1090-2120
dc.identifier.scopusidSCOPUS_ID:85199503608
dc.identifier.urihttps://doi.org/10.1016/j.bioorg.2024.107669
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/102861
dc.information.autorucEscuela de Química; Fuentealba Patiño, Denis Alberto; 0000-0003-4798-7204; 160255
dc.language.isoen
dc.nota.accesocontenido parcial
dc.revistaBioorganic Chemistry
dc.rightsacceso restringido
dc.subjectCathecol
dc.subjectInhibition
dc.subjectMacrophages cytoskeleton survival
dc.subjectNon-toxic α-syn oligomers
dc.subject.ddc510
dc.subject.deweyMatemática física y químicaes_ES
dc.subject.ods03 Good health and well-being
dc.subject.odspa03 Salud y bienestar
dc.titleRosmarinic acid turned α-syn oligomers into non-toxic species preserving microtubules in Raw 264.7 cells
dc.typeartículo
dc.volumen151
sipa.codpersvinculados160255
sipa.trazabilidadSCOPUS;2024-08-25
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