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Vicente-Zurdo, DavidAuthor

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October 24, 2024
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Neuroprotective mechanisms of multitarget 7-aminophenanthridin-6 (5H)-one derivatives against metal-induced amyloid proteins generation and aggregation

Publicated to: Food And Chemical Toxicology. 167 113264- - 2022-07-02 167(), DOI: 10.1016/j.fct.2022.113264

Authors:

Moyano, Paula; Vicente-Zurdo, David; Menendez, J Carlos; Gonzalez, Juan F; Rosales-Conrado, Noelia; del Pino, Javier
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Affiliations

Univ Complutense Madrid, Chem Pharmaceut Sci Dept, Pharm Sch, Avda Puerta Hierro s-n, Madrid 28040, Spain - Author
Univ Complutense Madrid, Chem Sci Sch, Analyt Chem Dept, Avda Puerta Hierro S-N, Madrid 28040, Spain - Author
Univ Complutense Madrid, Vet Sch, Pharmacol & Toxicol Dept, Avda Puerta Hierro S-N, Madrid 28040, Spain - Author
Univ Complutense, Fac Ciencias Quim, Dept Quim Analit, Madrid 28040, Spain - Author
Univ Complutense, Fac Farm, Dept Quim Ciencias Farmaceut, Unidad Quim Organ & Farmaceut, Madrid 28040, Spain - Author
Univ Complutense, Fac Vet, Dept Farmacol & Toxicol, Madrid 28040, Spain - Author
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Abstract

Brain's metals accumulation is associated with toxic proteins, like amyloid-proteins (A beta), 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 mu M) chemical ability to prevent metal-induced A beta proteins aggregation; the APH1-5 effect on HSP70 and proteasome 20S (P20S) expression, the metals effect on A beta formation and the involvement of HSP70 and P20S in the process, and the APH1-5 neuroprotective effects against A beta proteins (1 mu M) and metals in SN56 cells. Our results show that APH1-5 compounds chemically avoid metal-induced A beta proteins aggregation and induce HSP70 and P20S expression. Additionally, iron and cadmium induced A beta proteins formation through downregulation of HSP70 and P20S. Finally, APH1-5 compounds protected against A beta 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.
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Keywords

20s proteasomeA-betaAlpha-synucleinAlzheimer diseaseAmyloid beta-peptidesAmyloid proteinsAmyloidogenic proteinsAmyloidproteinCadmiumCell-deathCholinergic neuronsDiseasHeat-shock proteinsHsp70Hsp70 heat-shock proteinsHumansMatrix metalloproteinasesMetal neurotoxicityMetalneurotoxicityMetalsNeurodegenerative disordersNeuroprotective agentsPhenanthridonesProteasome 20sProteasome endopeptidase complexProteasome20sSn56 basal forebrain cholinergic neuronsSn56basalforebraincholinergicneurons

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Food And Chemical Toxicology due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2022, it was in position 20/94, thus managing to position itself as a Q1 (Primer Cuartil), in the category Toxicology.

Independientemente del impacto esperado determinado por el canal de difusión, es importante destacar el impacto real observado de la propia aportación.

Según las diferentes agencias de indexación, el número de citas acumuladas por esta publicación hasta la fecha 2026-01-20:

  • Google Scholar: 4
  • WoS: 2
  • Scopus: 2
  • Europe PMC: 2
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Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2026-01-20:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 9.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 9 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 7.
  • The number of mentions in news outlets: 1 (Altmetric).
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Awards linked to the item

This work was supported by the Spanish Ministry of Science and Innovation (RTI2018-097662-B-I00, PID2020-114714RB-I00) , the Community of Madrid and European Union from FSE and FEDER pro- grams (S2018/BAA-4393, AVANSECAL-II-CM) and Complutense University (PR26/16-16B) . David Vicente-Zurdo acknowledges the Spanish Ministry of Science, Innovation and Universities for a pre -doctoral grant (FPU18/00573) .
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