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Furanoditerpenes from Spongia (Spongia) tubulifera Display Mitochondrial-Mediated Neuroprotective Effects by Targeting Cyclophilin D
dc.contributor.author | Alvariño, Rebeca | |
dc.contributor.author | Alfonso, Amparo | |
dc.contributor.author | Pech-Puch, Dawrin | |
dc.contributor.author | Gegunde, Sandra | |
dc.contributor.author | Rodríguez, Jaime | |
dc.contributor.author | Vieytes, Mercedes R. | |
dc.contributor.author | Jiménez, Carlos | |
dc.contributor.author | Botana, Luis M. | |
dc.date.accessioned | 2024-06-28T10:58:24Z | |
dc.date.available | 2024-06-28T10:58:24Z | |
dc.date.issued | 2022-07-28 | |
dc.identifier.citation | Alvariño, R.; Alfonso, A.; Pech-Puch, D.; Gegunde, S.; Rodríguez, J.; Vieytes, M. R.; Jiménez, C.; Botana, L. M. Furanoditerpenes from Spongia (Spongia) Tubulifera Display Mitochondrial-Mediated Neuroprotective Effects by Targeting Cyclophilin D. ACS Chem. Neurosci. 2022, 13 (16), 2449–2463. https://doi.org/10.1021/acschemneuro.2c00208. | es_ES |
dc.identifier.issn | 1948-7193 | |
dc.identifier.uri | http://hdl.handle.net/2183/37543 | |
dc.description.abstract | [Abstract] Neuroprotective properties of five previously described furanoditerpenes 1–5, isolated from Spongia (Spongia) tubulifera, were evaluated in an in vitro oxidative stress model in SH-SY5Y cells. Dose–response treatments revealed that 1–5 improved cell survival at nanomolar concentrations through the restoration of mitochondrial membrane potential and the reduction of reactive oxygen species. Their ability to prevent the mitochondrial permeability transition pore opening was also assessed, finding that 4 and 5 inhibited the channel at 0.001 μM. This inhibition was accompanied by a decrease in the expression of cyclophilin D, the main regulator of the pore, which was also reduced by 1 and 2. However, the activation of ERK and GSK3β, upstream modulators of the channel, was not affected by compounds. Therefore, their ability to bind cyclophilin D was evaluated by surface plasmon resonance, observing that 2–5 presented equilibrium dissociation constants in the micromolar range. All compounds also showed affinity for cyclophilin A, being 1 selective toward this isoform, while 2 and 5 exhibited selectivity for cyclophilin D. When the effects on the intracellular expression of cyclophilins A–C were determined, it was found that only 1 decreased cyclophilin A, while cyclophilins B and C were diminished by most compounds, displaying enhanced effects under oxidative stress conditions. Results indicate that furanoditerpenes 1–5 have mitochondrial-mediated neuroprotective properties through direct interaction with cyclophilin D. Due to the important role of this protein in oxidative stress and inflammation, compounds are promising drugs for new therapeutic strategies against neurodegeneration. | es_ES |
dc.description.sponsorship | The research leading to these results has received funding from the following FEDER cofunded grants: from Conselleria de Cultura, Educacion e Ordenación Universitaria, Xunta de Galicia, GRC (ED431C 2021/01), and GRC2018/039; from the Ministerio de Ciencia e Innovación IISCIII/PI19/001248 and PID 2020-11262RB-C21; from European Union Interreg AlertoxNet EAPA-317-2016 and Interreg Agritox EAPA-998-2018 and H2020 778069-EMERTOX; and from BLUEBIOLAB (0474_BLUEBIOLAB_1_E), Programme INTERREG V A of Spain-Portugal (POCTEP). R.A. was supported by a postdoctoral fellowship from Xunta de Galicia (ED481B-2021-038), Spain. D.P-P. received a postdoctoral fellowship from the National Council of Science and Technology (CONACYT) of Mexico | es_ES |
dc.description.sponsorship | Xunta de Galicia; ED431C 2021/01 | es_ES |
dc.description.sponsorship | Xunta de Galicia; GRC2018/039 | es_ES |
dc.description.sponsorship | Xunta de Galicia; ED481B-2021-038 | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | American Chemical Society | es_ES |
dc.relation | info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PI19%2F01248/ES/NIVELES DE CICLOFILINAS COMO BIOMARCADORES DE ENFERMEDAD CORONARIA (CAD). EVALUACION DE INHIBIDORES ESPECIFICOS DE CICLOFILINAS COMO PROTECTORES CARDIOVASCULARES | es_ES |
dc.relation | info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-112626RB-C21/ES/DETOXIFICACION MAGNETICA DE MICROCISTINAS EN AGUA DULCE | es_ES |
dc.relation | info:eu-repo/grantAgreement/EC/H2020/778069 | es_ES |
dc.relation.uri | https://doi.org/10.1021/acschemneuro.2c00208 | es_ES |
dc.rights | Atribución 4.0 Internacional | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | Furanoditerpenes | es_ES |
dc.subject | Spongia (Spongia) tubulifera | es_ES |
dc.subject | Mitochondria | es_ES |
dc.subject | Cyclophilin | es_ES |
dc.subject | Neuroprotection | es_ES |
dc.subject | Oxidative stress | es_ES |
dc.title | Furanoditerpenes from Spongia (Spongia) tubulifera Display Mitochondrial-Mediated Neuroprotective Effects by Targeting Cyclophilin D | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.access | info:eu-repo/semantics/openAccess | es_ES |
UDC.journalTitle | ACS Chemical Neuroscience | es_ES |
UDC.volume | 13 | es_ES |
UDC.issue | 16 | es_ES |
UDC.startPage | 2449 | es_ES |
UDC.endPage | 2463 | es_ES |
dc.identifier.doi | 10.1021/acschemneuro.2c00208 |
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