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

Moyano, Paula; Vicente-Zurdo, David; Blázquez-Barbadillo, Cristina; Menéndez, J. Carlos; González, Juan F.; Rosales-Conrado, Noelia; Pino, Javier del

doi:10.1016/j.fct.2022.113264

Cited by 2 publications

(1 citation statement)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Paraquat increases phosphorylated-Tau and α-synuclein levels and decreases proteasome activity in the striatum of mice repeatedly exposed [ 54 ], suggesting that this effect could be mediated by proteasome dysfunction as well. Cd single treatment induced Aβ proteins accumulation through P20S inhibition in BF SN56 cholinergic neurons [ 243 ], and Cd single treatment was shown to induce the formation of prion proteins through proteasome inhibition in mouse neuronal cells [ 65 ]. Moreover, Mn, chlorpyrifos, and PQ have been reported to induce accumulation of p-Tau and Aβ proteins through reduced proteasome 20S activity after 1 day and 14 days of treatment in SN56 cells and primary hippocampal neurons [ 49 , 51 , 52 ], showing the participation of proteasome dysfunction in the accumulation of aberrant toxic proteins.…”

Section: Proteasome and Epsmentioning

confidence: 99%

Neurodegenerative Proteinopathies Induced by Environmental Pollutants: Heat Shock Proteins and Proteasome as Promising Therapeutic Tools

Moyano,

Sola,

Naval

et al. 2023

Pharmaceutics

Self Cite

View full text Add to dashboard Cite

Environmental pollutants’ (EPs) amount and diversity have increased in recent years due to anthropogenic activity. Several neurodegenerative diseases (NDs) are theorized to be related to EPs, as their incidence has increased in a similar way to human EPs exposure and they reproduce the main ND hallmarks. EPs induce several neurotoxic effects, including accumulation and gradual deposition of misfolded toxic proteins, producing neuronal malfunction and cell death. Cells possess different mechanisms to eliminate these toxic proteins, including heat shock proteins (HSPs) and the proteasome system. The accumulation and deleterious effects of toxic proteins are induced through HSPs and disruption of proteasome proteins’ homeostatic function by exposure to EPs. A therapeutic approach has been proposed to reduce accumulation of toxic proteins through treatment with recombinant HSPs/proteasome or the use of compounds that increase their expression or activity. Our aim is to review the current literature on NDs related to EP exposure and their relationship with the disruption of the proteasome system and HSPs, as well as to discuss the toxic effects of dysfunction of HSPs and proteasome and the contradictory effects described in the literature. Lastly, we cover the therapeutic use of developed drugs and recombinant proteasome/HSPs to eliminate toxic proteins and prevent/treat EP-induced neurodegeneration.

show abstract

Section: Proteasome and Epsmentioning

confidence: 99%

Neurodegenerative Proteinopathies Induced by Environmental Pollutants: Heat Shock Proteins and Proteasome as Promising Therapeutic Tools

Moyano,

Sola,

Naval

et al. 2023

Pharmaceutics

Self Cite

View full text Add to dashboard Cite

show abstract

Thyroid Hormone Neuroprotection Against Perfluorooctane Sulfonic Acid Cholinergic and Glutamatergic Disruption and Neurodegeneration Induction

Moyano,

Guzmán,

Flores

et al. 2024

Biomedicines

View full text Add to dashboard Cite

Background: Perfluorooctane sulfonic acid (PFOS), a widely used industrial chemical, was reported to induce memory and learning process dysfunction. Some studies tried to reveal the mechanisms that mediate these effects, but how they are produced is still unknown. Basal forebrain cholinergic neurons (BFCN) maintain cognitive function and their selective neurodegeneration induces cognitive decline, as observed in Alzheimer’s disease. PFOS was reported to disrupt cholinergic and glutamatergic transmissions and thyroid hormone action, which regulate cognitive processes and maintain BFCN viability. Objective/Methods: To evaluate PFOS neurodegenerative effects on BFCN and the mechanisms that mediate them, SN56 cells (a neuroblastoma cholinergic cell line from the basal forebrain) were treated with PFOS (0.1 µM to 40 µM) with or without thyroxine (T3; 15 nM), MK-801 (20 µM) or acetylcholine (ACh; 10 µM). Results: In the present study, we found that PFOS treatment (1 or 14 days) decreased thyroid receptor α (TRα) activity by decreasing its protein levels and increased T3 metabolism through increased deiodinase 3 (D3) levels. Further, we observed that PFOS treatment disrupted cholinergic transmission by decreasing ACh content through decreased choline acetyltransferase (ChAT) activity and protein levels and through decreasing muscarinic receptor 1 (M1R) binding and protein levels. PFOS also disrupted glutamatergic transmission by decreasing glutamate content through increased glutaminase activity and protein levels and through decreasing N-methyl-D-aspartate receptor subunit 1 (NMDAR1); effects mediated through M1R disruption. All these effects were mediated through decreased T3 activity and T3 supplementation partially restored to the normal state. Conclusions: These findings may assist in understanding how PFOS induces neurodegeneration, and the mechanisms involved, especially in BFCN, to explain the process that could lead to cognitive dysfunction and provide new therapeutic tools to treat and prevent its neurotoxic effects.

show abstract

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

Cited by 2 publications

References 65 publications

Neurodegenerative Proteinopathies Induced by Environmental Pollutants: Heat Shock Proteins and Proteasome as Promising Therapeutic Tools

Neurodegenerative Proteinopathies Induced by Environmental Pollutants: Heat Shock Proteins and Proteasome as Promising Therapeutic Tools

Thyroid Hormone Neuroprotection Against Perfluorooctane Sulfonic Acid Cholinergic and Glutamatergic Disruption and Neurodegeneration Induction

Contact Info

Product

Resources

About