RT Journal Article
T1 Neuroprotective mechanisms of multitarget 7-aminophenanthridin-6(5H)-one derivatives against metal-induced amyloid proteins generation and aggregation
A1 Moyano-Cires Ivanoff, Paula Viviana
A1 Vicente Zurdo, David
A1 Blázquez Barbadillo, Cristina
A1 Menéndez Ramos, José Carlos
A1 González Matilla, Juan Francisco
A1 Rosales Conrado, Noelia
A1 Pino Sans, Javier Del
AB Brain’s metals accumulation is associated with toxic proteins, like amyloid-proteins (Aβ), formation, accumulation, and aggregation, leading to neurodegeneration. Metals downregulate the correct folding, disaggregation, or degradation mechanisms of toxic proteins, as heat shock proteins (HSPs) and proteasome. The 7-amino-phenanthridin-6(5H)-one derivatives (APH) showed neuroprotective effects against metal-induced cell death through their antioxidant effect, independently of their chelating activity. However, additional neuroprotective mechanisms seem to be involved. We tested the most promising APH compounds (APH1-5, 10–100 μM) chemical ability to prevent metal-induced Aβ proteins aggregation; the APH1-5 effect on HSP70 and proteasome 20S (P20S) expression, the metals effect on Aβ formation and the involvement of HSP70 and P20S in the process, and the APH1-5 neuroprotective effects against Aβ proteins (1 μM) and metals in SN56 cells. Our results show that APH1-5 compounds chemically avoid metal-induced Aβ proteins aggregation and induce HSP70 and P20S expression. Additionally, iron and cadmium induced Aβ proteins formation through downregulation of HSP70 and P20S. Finally, APH1-5 compounds protected against Aβ proteins-induced neuronal cell death, reversing partially or completely this effect. These data may help to provide a new therapeutic approach against the neurotoxic effect induced by metals and other environmental pollutants, especially when mediated by toxic proteins.
PB Elsevier
SN 0278-6915
YR 2022
FD 2022-07-02
LK https://hdl.handle.net/20.500.14352/71773
UL https://hdl.handle.net/20.500.14352/71773
LA eng
NO CRUE-CSIC (Acuerdos Transformativos 2022)
NO Ministerio de Ciencia e Innovación (MICINN)
NO Comunidad de Madrid/FEDER
NO Universidad Complutense de Madrid
DS Docta Complutense
RD 4 abr 2025