RT Journal Article
T1 Furanoditerpenes from Spongia (Spongia) tubulifera Display Mitochondrial-Mediated Neuroprotective Effects by Targeting Cyclophilin D
A1 Alvariño Romero, Rebeca
A1 Alfonso Rancaño, María Amparo
A1 Pech Puch, Dawrin
A1 Gegunde Mosquera, Sandra
A1 Rodríguez González, Jaime
A1 Rodríguez Vieytes, Mercedes
A1 Jiménez González, Carlos
A1 Botana López, Luis Miguel
K1 Assays
K1 Cells
K1 Hydrocarbons
K1 Oxidative stress
K1 Peptides and proteins
K1 Furanoditerpenes
K1 Spongia (Spongia) tubulifera
K1 Mitochondria
K1 Cyclophilin
K1 Neuroprotection
K1 Oxidative stress
AB 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
PB ACS Publications
YR 2022
FD 2022
LK http://hdl.handle.net/10347/29683
UL http://hdl.handle.net/10347/29683
LA eng
NO ACS Chem. Neurosci. 2022, 13, 16, 2449–2463
NO 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
DS Minerva
RD 23 abr 2026