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2000
Volume 22, Issue 5
  • ISSN: 1567-2050
  • E-ISSN: 1875-5828

Abstract

Background

Quinolinic Acid (QA), a neurotoxic metabolite in the kynurenine pathway, contributes to neuronal damage, oxidative stress, and neuroinflammation, playing a key role in Alzheimer's Disease (AD) pathogenesis. This study investigates the neuroprotective potential of polyphenolic compounds, particularly lycopene and a Curcumin-Zinc (Cur-Zn) complex, using and approaches targeting the kynurenine pathway.

Methodology

This study evaluated the neuroprotective potential of lycopene and Cur-Zn complex using and approaches. Molecular docking was performed to assess their binding affinities with the kynurenine pathway enzymes, and neuroprotection assays on N2a cells measured their efficacy against QA-induced oxidative stress.

Results

Docking analysis revealed strong binding affinities of Cur-Zn and lycopene to IDO1 and KMO, with fitness scores of 143.11 and 126.41, respectively, indicating their potential as enzyme-specific inhibitors. Lycopene exhibited the most potent neuroprotective effect (IC50 = 0.63 µM), followed by Cur-Zn (1.59 µM). Both compounds significantly reduced QA-induced ROS levels, as confirmed by DCFDA fluorescence imaging. Additionally, they upregulated KAT and QPRT enzymes, promoting neuroprotective metabolite production.

Discussion

Lycopene and Cur-Zn effectively modulate key kynurenine pathway enzymes while mitigating oxidative stress, supporting their potential as neuroprotective agents. Although bisabolol and bromelain exhibited some efficacy, their effects were comparatively lower.

Conclusion

Lycopene and Cur-Zn are promising candidates for AD therapy, demonstrating not only anti-oxidant activity but also a capacity to minimise the neurotoxic effects of QA, offering a dual mechanism of action. Further, studies are needed to validate their therapeutic potential in neurodegenerative diseases.

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2025-11-07

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Exploring the Neuroprotective Potential of Polyphenolic Compounds in Mitigating Quinolinic Acid-Induced Neurotoxicity in Alzheimer's Disease
Curr Alzheimer Res 22, 384 (2025); https://doi.org/10.2174/0115672050383383250529100802
/content/journals/car/10.2174/0115672050383383250529100802
/content/journals/car/10.2174/0115672050383383250529100802
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  • Article Type:     Research Article
Keyword(s): Alzheimer's disease; kynurenine pathway; neurotoxic effects; polyphenols; quinolinic acid; tryptophan pathway

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