Author | dc.contributor.author | González, Camila | |
Author | dc.contributor.author | Cartagena, Constanza | |
Author | dc.contributor.author | Caballero, Leonardo | |
Author | dc.contributor.author | Melo, Francisco | |
Author | dc.contributor.author | Areche Medina, Carlos Alberto | |
Author | dc.contributor.author | Cornejo, Alberto | |
Admission date | dc.date.accessioned | 2021-11-24T20:08:45Z | |
Available date | dc.date.available | 2021-11-24T20:08:45Z | |
Publication date | dc.date.issued | 2021 | |
Cita de ítem | dc.identifier.citation | Molecules 2021, 26, 3760. | es_ES |
Identifier | dc.identifier.other | 10.3390/molecules26123760 | |
Identifier | dc.identifier.uri | https://repositorio.uchile.cl/handle/2250/182873 | |
Abstract | dc.description.abstract | Neurodegenerative disorders, including Tauopathies that involve tau protein, base their
pathological mechanism on forming proteinaceous aggregates, which has a deleterious effect on cells
triggering an inflammatory response. Moreover, tau inhibitors can exert their mechanism of action
through noncovalent and covalent interactions. Thus, Michael’s addition appears as a feasible type
of interaction involving an , unsaturated carbonyl moiety to avoid pathological confirmation and
further cytotoxicity. Moreover, we isolated three compounds from Antarctic lichens Cladonia cariosa
and Himantormia lugubris: protolichesterinic acid (1), fumarprotocetraric acid (2), and lichesterinic
acid (3). The maleimide cysteine labeling assay showed that compounds 1, 2, and 3 inhibit at 50 M,
but compounds 2 and 3 are statistically significant. Based on its inhibition capacity, we decided to
test compound 2 further. Thus, our results suggest that compound 2 remodel soluble oligomers and
diminish sheet content, as demonstrated through ThT experiments. Hence, we added externally
treated oligomers with compound 2 to demonstrate that they are harmless in cell culture. First, the
morphology of cells in the presence of aggregates does not suffer evident changes compared to the
control. Additionally, the externally added aggregates do not provoke a substantial LDH release
compared to the control, indicating that treated oligomers do not provoke membrane damage in cell
culture compared with aggregates alone. Thus, in the present work, we demonstrated that Michael’s
acceptors found in lichens could serve as a scaffold to explore different mechanisms of action to turn
tau aggregates into harmless species. | es_ES |
Patrocinador | dc.description.sponsorship | Instituto Antartico Chileno (INACH) RT_18-19
ANID-Chile
Comision Nacional de Investigacion Cientifica y Tecnologica (CONICYT)
CONICYT FONDECYT 1201013
Fondequip EQM 130149
EQM 170111
Dicyt-Usach 041831MH | es_ES |
Lenguage | dc.language.iso | en | es_ES |
Publisher | dc.publisher | MDPI | es_ES |
Type of license | dc.rights | Attribution-NonCommercial-NoDerivs 3.0 United States | * |
Link to License | dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/us/ | * |
Source | dc.source | Molecules | es_ES |
Keywords | dc.subject | Lichens | es_ES |
Keywords | dc.subject | Tauopathies | es_ES |
Keywords | dc.subject | Alpha,beta carbonyl group | es_ES |
Keywords | dc.subject | Inhibitors | es_ES |
Keywords | dc.subject | Aggregates | es_ES |
Keywords | dc.subject | Cytotoxicity | es_ES |
Título | dc.title | The fumarprotocetraric acid inhibits tau covalently, avoiding cytotoxicity of aggregates in cells | es_ES |
Document type | dc.type | Artículo de revista | es_ES |
dc.description.version | dc.description.version | Versión publicada - versión final del editor | es_ES |
dcterms.accessRights | dcterms.accessRights | Acceso abierto | es_ES |
Cataloguer | uchile.catalogador | cfr | es_ES |
Indexation | uchile.index | Artículo de publícación WoS | es_ES |
Indexation | uchile.index | Artículo de publicación SCOPUS | es_ES |