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Circulating (Poly)phenol Metabolites : Neuroprotection in a 3D Cell Model of Parkinson's Disease

Circulating (Poly)phenol Metabolites : Neuroprotection in a 3D Cell Model of Parkinson's Disease

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CARECHO, Rafael, Inês FIGUEIRA, Ana Paula TERRASSO, Joana GODINHO-PEREIRA, Catarina DE OLIVEIRA SEQUEIRA, Sofia Azeredo PEREIRA, Dragan MILENKOVIC, Marcel LEIST, Catarina BRITO, Cláudia NUNES DOS SANTOS, 2022. Circulating (Poly)phenol Metabolites : Neuroprotection in a 3D Cell Model of Parkinson's Disease. In: Molecular Nutrition and Food Research. Wiley. 66(21), 2100959. ISSN 1613-4125. eISSN 1613-4133. Available under: doi: 10.1002/mnfr.202100959

@article{Carecho2022Circu-56361, title={Circulating (Poly)phenol Metabolites : Neuroprotection in a 3D Cell Model of Parkinson's Disease}, year={2022}, doi={10.1002/mnfr.202100959}, number={21}, volume={66}, issn={1613-4125}, journal={Molecular Nutrition and Food Research}, author={Carecho, Rafael and Figueira, Inês and Terrasso, Ana Paula and Godinho-Pereira, Joana and de Oliveira Sequeira, Catarina and Pereira, Sofia Azeredo and Milenkovic, Dragan and Leist, Marcel and Brito, Catarina and Nunes Dos Santos, Cláudia}, note={Article Number: 2100959} }

Terrasso, Ana Paula Godinho-Pereira, Joana Carecho, Rafael eng 2022-01-26T10:11:43Z de Oliveira Sequeira, Catarina Nunes Dos Santos, Cláudia Leist, Marcel Pereira, Sofia Azeredo Terrasso, Ana Paula Pereira, Sofia Azeredo Brito, Catarina Circulating (Poly)phenol Metabolites : Neuroprotection in a 3D Cell Model of Parkinson's Disease 2022 Carecho, Rafael de Oliveira Sequeira, Catarina 2022-01-26T10:11:43Z Milenkovic, Dragan Godinho-Pereira, Joana Leist, Marcel Nunes Dos Santos, Cláudia Milenkovic, Dragan Scope<br />Diets rich in (poly)phenols have been associated with positive effects on neurodegenerative disorders, such as Parkinson's disease (PD). Several low-molecular weight (poly)phenol metabolites (LMWPM) are found in the plasma after consumption of (poly)phenol-rich food. It is expected that LMWPM, upon reaching the brain, may have beneficial effects against both oxidative stress and neuroinflammation, and possibly attenuate cell death mechanisms relate to the loss of dopaminergic neurons in PD.<br /><br />Methods and Results<br />This study investigates the neuroprotective potential of two blood-brain barrier permeant LMWPM, catechol-O-sulfate (cat-sulf), and pyrogallol-O-sulfate (pyr-sulf), in a human 3D cell model of PD. Neurospheroids were generated from LUHMES neuronal precursor cells and challenged by 1-methyl-4-phenylpyridinium (MPP<sup>+</sup>) to induce neuronal stress. LMWPM pretreatments were differently neuroprotective towards MPP<sup>+</sup> insult, presenting distinct effects on the neuronal transcriptome. Particularly, cat-sulf pretreatment appeared to boost counter-regulatory defense mechanisms (preconditioning). When MPP<sup>+</sup> is applied, both LMWPM positively modulated glutathione metabolism and heat-shock response, as also favorably shifting the balance of pro/anti-apoptotic proteins.<br /><br />Conclusions<br />Our findings point to the potential of LMWPM to trigger molecular mechanisms that help dopaminergic neurons to cope with a subsequent toxic insult. They are promising molecules to be further explored in the context of preventing and attenuating parkinsonian neurodegeneration. Figueira, Inês Brito, Catarina Figueira, Inês Attribution 4.0 International

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