Corinne ANDRE-MIRAL
Professeur Université
section 32
| Équipe : |
Thèmes de recherche
Utilisation d’enzymes pour le développement de nouvelles voies de synthèse biocompatibles.
Mes travaux de recherches s’appuient à la fois sur un savoir-faire et un domaine d’expertise spécifique à l’interface chimie-biologie. Les thématiques de recherche que je développe se situent dans le domaine de la biocatalyse et de l’ingénierie moléculaire et ont pour principal objectif le développement de nouveaux outils enzymatiques au service de la glycobiologie pour la synthèse d’oligosaccharides et de glycoconjugués d’intérêt thérapeutique. L’ensemble des projets de recherche que je mène un caractère très pluridisciplinaire associant biocatalyse, enzymologie, biochimie, biologie moléculaire et bioinformatique.
Projets
Parcours universitaire
2013 Habilitation à Diriger des Recherches
Université de Nantes
Développement de nouveaux outils chimiques et enzymatiques au service de la glycobiologie pour la synthèse de glycoconjugués.
1998 Post-doctorat
Department of Chemistry – Université de Warwick (UK)
Synthèse chimioenzymatique de carbohydrates biologiquement actifs et d’analogues : obtention d’oligosaccharides et de glycolipides sulfatés.
1997 Doctorat
Laboratoire de Synthèse Et Etudes de Systèmes à Intérêt Biologique (SEESIB – UMR 6504) – Université Blaise Pascal (Clermont-Ferrand)
La transcétolase et la fructose-1,6-bisphosphate aldolase: outils complémentaires pour la synthèse enzymatique de monosaccharides à partir de 3,4-dihydroxybutyraldéhydes.
Publications
3 publications
Schimith, Lucia Emanueli; da Silva, Vitória Machado; da Costa-Silva, Dennis Guilherme; Monteiro, Linda Karolynne Seregni; Muccillo-Baisch, Ana Luiza; André-Miral, Corinne; Hort, Mariana Appel
Preclinical toxicological assessment of polydatin in zebrafish model Article de journal
Dans: Drug Chem Toxicol, p. 1–10, 2024, ISSN: 1525-6014.
@article{pmid38311823,
title = {Preclinical toxicological assessment of polydatin in zebrafish model},
author = {Lucia Emanueli Schimith and Vitória Machado da Silva and Dennis Guilherme da Costa-Silva and Linda Karolynne Seregni Monteiro and Ana Luiza Muccillo-Baisch and Corinne André-Miral and Mariana Appel Hort},
url = {https://hal.science/hal-04610793v1},
doi = {10.1080/01480545.2024.2311287},
issn = {1525-6014},
year = {2024},
date = {2024-02-01},
urldate = {2024-02-01},
journal = {Drug Chem Toxicol},
pages = {1--10},
abstract = {Polydatin (3,4',5-trihydroxystilbene-3-β-D-glucoside, piceid), a natural stilbenoid found in different plant sources, has gained increasing attention for its potential health benefits. However, prior to its widespread adoption in human therapeutics and consumer products, a comprehensive investigation of its toxicological effects is crucial. In this study, the toxicity of polydatin was investigated in a developmental toxicity test using zebrafish () as a valuable model for preclinical assessments. We employed the Fish Embryo Test (FET test - OECD n°236) to investigate the effects of polydatin on survival, hatchability, development, and behavior of zebrafish embryo-larval stage. Remarkably, the results demonstrated that polydatin up to 435 μM showed no toxicity. Throughout the exposure period, zebrafish embryos exposed to polydatin exhibited normal development, with no significant mortality observed. Furthermore, hatching success and heartbeat rate were unaffected, and no morphological abnormalities were identified, signifying a lack of teratogenic effects and cardiotoxicity. Locomotion activity assessment revealed normal swimming patterns and response to stimuli, indicating no neurotoxic effects. Our study provides valuable insights into the toxicological profile of polydatin, suggesting that it may offer potential therapeutic benefits under a considerable concentration range. In addition, zebrafish model proves to be an efficient system for early-stage toxicological screening, guiding further investigations into the secure utilization of polydatin for human health and wellness.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Polydatin (3,4',5-trihydroxystilbene-3-β-D-glucoside, piceid), a natural stilbenoid found in different plant sources, has gained increasing attention for its potential health benefits. However, prior to its widespread adoption in human therapeutics and consumer products, a comprehensive investigation of its toxicological effects is crucial. In this study, the toxicity of polydatin was investigated in a developmental toxicity test using zebrafish () as a valuable model for preclinical assessments. We employed the Fish Embryo Test (FET test - OECD n°236) to investigate the effects of polydatin on survival, hatchability, development, and behavior of zebrafish embryo-larval stage. Remarkably, the results demonstrated that polydatin up to 435 μM showed no toxicity. Throughout the exposure period, zebrafish embryos exposed to polydatin exhibited normal development, with no significant mortality observed. Furthermore, hatching success and heartbeat rate were unaffected, and no morphological abnormalities were identified, signifying a lack of teratogenic effects and cardiotoxicity. Locomotion activity assessment revealed normal swimming patterns and response to stimuli, indicating no neurotoxic effects. Our study provides valuable insights into the toxicological profile of polydatin, suggesting that it may offer potential therapeutic benefits under a considerable concentration range. In addition, zebrafish model proves to be an efficient system for early-stage toxicological screening, guiding further investigations into the secure utilization of polydatin for human health and wellness.
Goux, Marine; Demonceaux, Marie; Hendrickx, Johann; Solleux, Claude; Lormeau, Emilie; Fredslund, Folmer; Tezé, David; Offmann, Bernard; André-Miral, Corinne
Sucrose phosphorylase from Alteromonas mediterranea: structural insight into the regioselective α-glucosylation of (+)-catechin Article de journal
Dans: Biochimie, 2024.
@article{Goux2023.04.11.536264,
title = {Sucrose phosphorylase from Alteromonas mediterranea: structural insight into the regioselective α-glucosylation of (+)-catechin},
author = {Marine Goux and Marie Demonceaux and Johann Hendrickx and Claude Solleux and Emilie Lormeau and Folmer Fredslund and David Tezé and Bernard Offmann and Corinne André-Miral},
url = {https://www.biorxiv.org/content/10.1101/2023.04.11.536264v2
hal-04095395v2 },
doi = {10.1016/j.biochi.2024.01.004},
year = {2024},
date = {2024-01-09},
urldate = {2024-01-09},
journal = {Biochimie},
publisher = {Cold Spring Harbor Laboratory},
abstract = {Sucrose phosphorylases, through transglycosylation reactions, are interesting enzymes that can transfer regioselectively glucose from sucrose, the donor substrate, onto acceptors like flavonoids to form glycoconjugates and hence modulate their solubility and bioactivity. Here, we report for the first time the structure of sucrose phosphorylase from the marine bacteria Alteromonas mediterranea (AmSP) and its enzymatic properties. Kinetics of sucrose hydrolysis and transglucosylation capacities on (+)-catechin were investigated. Wild-type enzyme (AmSP-WT) displayed high hydrolytic activity on sucrose and was devoid of transglucosylation activity on (+)-catechin. Two variants, AmSP-Q353F and AmSP-P140D catalysed the regiospecific transglucosylation of (+)-catechin: 89 % of a novel compound (+)-catechin-4′-O-α-d-glucopyranoside (CAT-4′) for AmSP-P140D and 92 % of (+)-catechin-3′-O-α-d-glucopyranoside (CAT-3′) for AmSP-Q353F. The compound CAT-4′ was fully characterized by NMR and mass spectrometry. An explanation for this difference in regiospecificity was provided at atomic level by molecular docking simulations: AmSP-P140D was found to preferentially bind (+)-catechin in a mode that favours glucosylation on its hydroxyl group in position 4′ while the binding mode in AmSP-Q353F favoured glucosylation on its hydroxyl group in position 3’.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Sucrose phosphorylases, through transglycosylation reactions, are interesting enzymes that can transfer regioselectively glucose from sucrose, the donor substrate, onto acceptors like flavonoids to form glycoconjugates and hence modulate their solubility and bioactivity. Here, we report for the first time the structure of sucrose phosphorylase from the marine bacteria Alteromonas mediterranea (AmSP) and its enzymatic properties. Kinetics of sucrose hydrolysis and transglucosylation capacities on (+)-catechin were investigated. Wild-type enzyme (AmSP-WT) displayed high hydrolytic activity on sucrose and was devoid of transglucosylation activity on (+)-catechin. Two variants, AmSP-Q353F and AmSP-P140D catalysed the regiospecific transglucosylation of (+)-catechin: 89 % of a novel compound (+)-catechin-4′-O-α-d-glucopyranoside (CAT-4′) for AmSP-P140D and 92 % of (+)-catechin-3′-O-α-d-glucopyranoside (CAT-3′) for AmSP-Q353F. The compound CAT-4′ was fully characterized by NMR and mass spectrometry. An explanation for this difference in regiospecificity was provided at atomic level by molecular docking simulations: AmSP-P140D was found to preferentially bind (+)-catechin in a mode that favours glucosylation on its hydroxyl group in position 4′ while the binding mode in AmSP-Q353F favoured glucosylation on its hydroxyl group in position 3’.
Graton, Jérôme; Goupille, Anaïs; Ferré, Tanguy; Offmann, Bernard; André-Miral, Corinne; Questel, Jean-Yves Le
Antioxidant properties of catechin and its 3′O-α-glucoside: Insights from computational chemistry calculations Article de journal
Dans: Computational and Theoretical Chemistry, vol. 1236, p. 114608, 2024, ISSN: 2210-271X.
@article{GRATON2024114608,
title = {Antioxidant properties of catechin and its 3′O-α-glucoside: Insights from computational chemistry calculations},
author = {Jérôme Graton and Anaïs Goupille and Tanguy Ferré and Bernard Offmann and Corinne André-Miral and Jean-Yves Le Questel},
url = {https://www.sciencedirect.com/science/article/pii/S2210271X24001476
https://hal.science/hal-04610796v1},
doi = {https://doi.org/10.1016/j.comptc.2024.114608},
issn = {2210-271X},
year = {2024},
date = {2024-01-01},
urldate = {2024-01-01},
journal = {Computational and Theoretical Chemistry},
volume = {1236},
pages = {114608},
abstract = {Density functional theory (DFT) calculations were used to investigate the conformational landscape of catechin and one of its main glucoside derivative (catechin-3′ O- α −glucopyranoside), and to determine the corresponding antioxidant properties. These investigations were carried out in benzene and water using the SMD universal continuum solvation model. Both properties were found to be significantly affected. The structures are characterized in both solvents by strong intramolecular hydrogen bonds (IMHB). In an apolar environment, Hydrogen Atom Transfer (HAT) is by far favored whereas in water the Sequential Proton Loss Electron Transfer (SPLET) mechanism is strongly preferred. In benzene, the catechin fragment has the best antioxidant character (from 27 kJ/mole) whereas in polar surroundings, the glucoside derivative has a slightly better antiradical activity (from 5 kJ/mole). Our results confirm the key role of the 3′-OH and 4′-OH groups of the catechole ring in these properties.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Density functional theory (DFT) calculations were used to investigate the conformational landscape of catechin and one of its main glucoside derivative (catechin-3′ O- α −glucopyranoside), and to determine the corresponding antioxidant properties. These investigations were carried out in benzene and water using the SMD universal continuum solvation model. Both properties were found to be significantly affected. The structures are characterized in both solvents by strong intramolecular hydrogen bonds (IMHB). In an apolar environment, Hydrogen Atom Transfer (HAT) is by far favored whereas in water the Sequential Proton Loss Electron Transfer (SPLET) mechanism is strongly preferred. In benzene, the catechin fragment has the best antioxidant character (from 27 kJ/mole) whereas in polar surroundings, the glucoside derivative has a slightly better antiradical activity (from 5 kJ/mole). Our results confirm the key role of the 3′-OH and 4′-OH groups of the catechole ring in these properties.
2 publications
Demonceaux, Marie; Goux, Marine; Schimith, Lucia Emanueli; Santos, Michele Goulart Dos; Hendrickx, Johann; Offmann, Bernard; André-Miral, Corinne
Enzymatic synthesis, characterization and molecular docking of a new functionalized polyphenol: Resveratrol-3, 4’-⍺-diglucoside Article de journal
Dans: Results in Chemistry, p. 100956, 2023.
@article{demonceaux2023enzymatic,
title = {Enzymatic synthesis, characterization and molecular docking of a new functionalized polyphenol: Resveratrol-3, 4’-⍺-diglucoside},
author = {Marie Demonceaux and Marine Goux and Lucia Emanueli Schimith and Michele Goulart Dos Santos and Johann Hendrickx and Bernard Offmann and Corinne André-Miral},
url = {https://www.sciencedirect.com/science/article/pii/S2211715623001959},
doi = {10.1016/j.rechem.2023.100956},
year = {2023},
date = {2023-05-16},
urldate = {2023-05-16},
journal = {Results in Chemistry},
pages = {100956},
publisher = {Elsevier},
abstract = {Transglucosylation of resveratrol by the Q345F variant of sucrose phosphorylase from Bifidobacterium adolescentis (BaSP) was extensively studied during the last decade. Indeed, Q345F is able to catalyze the synthesis of resveratrol-3-O-⍺-D-glucoside (RES-3) with yield up to 97% using a cost-effective glucosyl donor, sucrose (Kraus et al., Chemical Communications, 53(90), 12182–12184 (2017)). Despite the fact that two further products were detectable in low amounts after glucoside synthesis, they were never identified. Here, we isolated and fully characterized one of those two minor products: resveratrol-3,4′-O-⍺-D-diglucoside (RES-3,4′). This original compound had never been described before. Using bioinformatics models, we successfully explained the formation of this diglucosylated product. Indeed, with RES-3 as acceptor substrate, Q345F is able to transfer a glucosyl moiety in position 4′-OH, what had been reported as impossible in the literature. The low yield observed is due to the steric hindrance into the catalytic site between RES-3 and residues Tyr132 and Tyr344. Nevertheless, the substrate orientation in the active site is favored by stabilizing interactions. Ring A of RES-3 bearing the diol moiety is stabilized by hydrogen bonds with residues Asp50, Arg135, Asn347 and Arg399. Hydroxyl group OH-4′ shares hydrogen bonds with the catalytic residues Asp192 and Glu232. Multiple hydrophobic contacts complete the stabilization of the substrate to favor the glucosylation at position 4′. Understanding of the mechanisms allowing the glucosylation at position 4′ of resveratrol will help the development of enzymatic tools to target and control the enzymatic synthesis of original ⍺-glucosylated polyphenols with high added value and better biodisponibility.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Transglucosylation of resveratrol by the Q345F variant of sucrose phosphorylase from Bifidobacterium adolescentis (BaSP) was extensively studied during the last decade. Indeed, Q345F is able to catalyze the synthesis of resveratrol-3-O-⍺-D-glucoside (RES-3) with yield up to 97% using a cost-effective glucosyl donor, sucrose (Kraus et al., Chemical Communications, 53(90), 12182–12184 (2017)). Despite the fact that two further products were detectable in low amounts after glucoside synthesis, they were never identified. Here, we isolated and fully characterized one of those two minor products: resveratrol-3,4′-O-⍺-D-diglucoside (RES-3,4′). This original compound had never been described before. Using bioinformatics models, we successfully explained the formation of this diglucosylated product. Indeed, with RES-3 as acceptor substrate, Q345F is able to transfer a glucosyl moiety in position 4′-OH, what had been reported as impossible in the literature. The low yield observed is due to the steric hindrance into the catalytic site between RES-3 and residues Tyr132 and Tyr344. Nevertheless, the substrate orientation in the active site is favored by stabilizing interactions. Ring A of RES-3 bearing the diol moiety is stabilized by hydrogen bonds with residues Asp50, Arg135, Asn347 and Arg399. Hydroxyl group OH-4′ shares hydrogen bonds with the catalytic residues Asp192 and Glu232. Multiple hydrophobic contacts complete the stabilization of the substrate to favor the glucosylation at position 4′. Understanding of the mechanisms allowing the glucosylation at position 4′ of resveratrol will help the development of enzymatic tools to target and control the enzymatic synthesis of original ⍺-glucosylated polyphenols with high added value and better biodisponibility.
Demonceaux, Marie; Goux, Marine; Hendrickx, Johann; Solleux, Claude; Cadet, Frédéric; Lormeau, Émilie; Offmann, Bernard; André-Miral, Corinne
Regioselective glucosylation of (+)-catechin using a new variant of sucrose phosphorylase from Bifidobacterium adolescentis Article de journal
Dans: Organic & Biomolecular Chemistry, vol. 21, no. 11, p. 2307–2311, 2023.
@article{demonceaux2023regioselective,
title = {Regioselective glucosylation of (+)-catechin using a new variant of sucrose phosphorylase from Bifidobacterium adolescentis},
author = {Marie Demonceaux and Marine Goux and Johann Hendrickx and Claude Solleux and Frédéric Cadet and Émilie Lormeau and Bernard Offmann and Corinne André-Miral},
doi = {10.1039/D3OB00191A},
year = {2023},
date = {2023-02-22},
urldate = {2023-02-22},
journal = {Organic & Biomolecular Chemistry},
volume = {21},
number = {11},
pages = {2307--2311},
publisher = {Royal Society of Chemistry},
abstract = {Mutation Q345F in sucrose phosphorylase from Bifidobacterium adolescentis (BaSP) has shown to allow efficient (+)-catechin glucosylation yielding a regioisomeric mixture: (+)-catechin-3′-O-α-D-glucopyranoside, (+)-catechin-5-O-α-D-glucopyranoside and (+)-catechin-3′,5-O-α-D-diglucopyranoside with a ratio of 51 : 25 : 24. Here, we efficiently increased the control of (+)-catechin glucosylation regioselectivity with a new variant Q345F/P134D. The same products were obtained with a ratio of 82 : 9 : 9. Thanks to bioinformatics models, we successfully explained the glucosylation favoured at the OH-3′ position due to the mutation P134D.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Mutation Q345F in sucrose phosphorylase from Bifidobacterium adolescentis (BaSP) has shown to allow efficient (+)-catechin glucosylation yielding a regioisomeric mixture: (+)-catechin-3′-O-α-D-glucopyranoside, (+)-catechin-5-O-α-D-glucopyranoside and (+)-catechin-3′,5-O-α-D-diglucopyranoside with a ratio of 51 : 25 : 24. Here, we efficiently increased the control of (+)-catechin glucosylation regioselectivity with a new variant Q345F/P134D. The same products were obtained with a ratio of 82 : 9 : 9. Thanks to bioinformatics models, we successfully explained the glucosylation favoured at the OH-3′ position due to the mutation P134D.
2 publications
Schimith, Lucia E; Santos, Michele G Dos; Arbo, Bruno D; André-Miral, Corinne; Muccillo-Baisch, Ana L; Hort, Mariana A
Polydatin as a therapeutic alternative for central nervous system disorders: A systematic review of animal studies Article de journal
Dans: Phytotherapy Research, vol. 36, no. 7, p. 2852–2877, 2022.
@article{schimith2022polydatin,
title = {Polydatin as a therapeutic alternative for central nervous system disorders: A systematic review of animal studies},
author = {Lucia E Schimith and Michele G Dos Santos and Bruno D Arbo and Corinne André-Miral and Ana L Muccillo-Baisch and Mariana A Hort},
url = {https://onlinelibrary.wiley.com/doi/10.1002/ptr.7497},
doi = {10.1002/ptr.7497},
year = {2022},
date = {2022-05-25},
urldate = {2022-05-25},
journal = {Phytotherapy Research},
volume = {36},
number = {7},
pages = {2852--2877},
publisher = {Wiley Online Library},
abstract = {Polydatin, or piceid, is a natural stilbene found in grapes, peanuts, and wines. Polydatin presents pharmacological activities, including neuroprotective properties, exerting preventive and/or therapeutic effects in central nervous system (CNS) disorders. In the present study, we summarize and discuss the neuroprotective effects of polydatin in CNS disorders and related pathological conditions in preclinical animal studies. A systematic review was performed by searching online databases, returning a total of 110 records, where 27 articles were selected and discussed here. The included studies showed neuroprotective effects of polydatin in experimental models of neurological disorders, including cerebrovascular disorders, Parkinson's disease, traumatic brain injuries, diabetic neuropathy, glioblastoma, and neurotoxicity induced by chemical agents. Most studies were focused on stroke (22.2%) and conducted in male rodents. The intervention protocol with polydatin was mainly acute (66.7%), with postdamage induction treatment being the most commonly used regimen (55.2%). Overall, polydatin ameliorated behavioral dysfunctions and/or promoted neurological function by virtue of its antioxidant and antiinflammatory properties. In summary, this review offers important scientific evidence for the neuroprotective effects and distinct pharmacological mechanisms of polydatin that not only enhances the present understanding but is also useful for the development of future preclinical and clinical investigations.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Polydatin, or piceid, is a natural stilbene found in grapes, peanuts, and wines. Polydatin presents pharmacological activities, including neuroprotective properties, exerting preventive and/or therapeutic effects in central nervous system (CNS) disorders. In the present study, we summarize and discuss the neuroprotective effects of polydatin in CNS disorders and related pathological conditions in preclinical animal studies. A systematic review was performed by searching online databases, returning a total of 110 records, where 27 articles were selected and discussed here. The included studies showed neuroprotective effects of polydatin in experimental models of neurological disorders, including cerebrovascular disorders, Parkinson's disease, traumatic brain injuries, diabetic neuropathy, glioblastoma, and neurotoxicity induced by chemical agents. Most studies were focused on stroke (22.2%) and conducted in male rodents. The intervention protocol with polydatin was mainly acute (66.7%), with postdamage induction treatment being the most commonly used regimen (55.2%). Overall, polydatin ameliorated behavioral dysfunctions and/or promoted neurological function by virtue of its antioxidant and antiinflammatory properties. In summary, this review offers important scientific evidence for the neuroprotective effects and distinct pharmacological mechanisms of polydatin that not only enhances the present understanding but is also useful for the development of future preclinical and clinical investigations.
Santos, Michele Goulart Dos; Schimith, Lucia Emanueli; André-Miral, Corinne; Muccillo-Baisch, Ana Luiza; Arbo, Bruno Dutra; Hort, Mariana Appel
Neuroprotective effects of resveratrol in in vivo and in vitro experimental models of Parkinson’s disease: A systematic review Article de journal
Dans: Neurotoxicity Research, p. 1–27, 2022.
@article{dos2022neuroprotective,
title = {Neuroprotective effects of resveratrol in in vivo and in vitro experimental models of Parkinson’s disease: A systematic review},
author = {Michele Goulart Dos Santos and Lucia Emanueli Schimith and Corinne André-Miral and Ana Luiza Muccillo-Baisch and Bruno Dutra Arbo and Mariana Appel Hort},
editor = {Springer},
doi = {10.1007/s12640-021-00450-x},
year = {2022},
date = {2022-01-12},
urldate = {2022-01-12},
journal = {Neurotoxicity Research},
pages = {1--27},
publisher = {Springer},
abstract = {Parkinson’s disease (PD) is currently the second most common neurodegenerative disease, being characterized by motor and non-motor symptoms. The therapeutic options available for its treatment are limited, do not slow the progression of the disease, and have serious side effects. For this reason, many studies have sought to find compounds with neuroprotective properties that bring additional benefits to current therapy. In this context, resveratrol is a phenolic compound, found in many plant species, capable of crossing the blood–brain barrier and having multiple biological properties. Experimental studies in vitro and in vivo have shown that it can prevent or slow the progression of a variety of diseases, including PD. In this systematic review, we summarize the effects of resveratrol in experimental in vivo and in vitro models of PD and discuss the molecular mechanisms involved in its action. The bibliographic search was performed in the databases of PubMed, Web of Science, SciELO, and Google Scholar, and based on the inclusion criteria, 41 articles were selected and discussed. Most of the included studies have demonstrated neuroprotective effects of resveratrol. In general, resveratrol prevented behavioral and/or neurological disorders, improved antioxidant defenses, reduced neuroinflammatory processes, and inhibited apoptosis. In summary, this systematic review offers important scientific evidence of neuroprotective effects of resveratrol in PD and also provide valuable information about its mechanism of action that can support future clinical studies.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Parkinson’s disease (PD) is currently the second most common neurodegenerative disease, being characterized by motor and non-motor symptoms. The therapeutic options available for its treatment are limited, do not slow the progression of the disease, and have serious side effects. For this reason, many studies have sought to find compounds with neuroprotective properties that bring additional benefits to current therapy. In this context, resveratrol is a phenolic compound, found in many plant species, capable of crossing the blood–brain barrier and having multiple biological properties. Experimental studies in vitro and in vivo have shown that it can prevent or slow the progression of a variety of diseases, including PD. In this systematic review, we summarize the effects of resveratrol in experimental in vivo and in vitro models of PD and discuss the molecular mechanisms involved in its action. The bibliographic search was performed in the databases of PubMed, Web of Science, SciELO, and Google Scholar, and based on the inclusion criteria, 41 articles were selected and discussed. Most of the included studies have demonstrated neuroprotective effects of resveratrol. In general, resveratrol prevented behavioral and/or neurological disorders, improved antioxidant defenses, reduced neuroinflammatory processes, and inhibited apoptosis. In summary, this systematic review offers important scientific evidence of neuroprotective effects of resveratrol in PD and also provide valuable information about its mechanism of action that can support future clinical studies.
3 publications
Teze, David; Coines, Joan; Raich, Lluís; Kalichuk, Valentina; Solleux, Claude; Tellier, Charles; André-Miral, Corinne; Svensson, Birte; Rovira, Carme
A Single Point Mutation Converts GH84 O-GlcNAc Hydrolases into Phosphorylases: Experimental and Theoretical Evidence Article de journal
Dans: Journal of the American Chemical Society, vol. 142, no. 5, p. 2120–2124, 2020, ISSN: 15205126.
@article{Teze2020,
title = {A Single Point Mutation Converts GH84 O-GlcNAc Hydrolases into Phosphorylases: Experimental and Theoretical Evidence},
author = {David Teze and Joan Coines and Lluís Raich and Valentina Kalichuk and Claude Solleux and Charles Tellier and Corinne André-Miral and Birte Svensson and Carme Rovira},
doi = {10.1021/jacs.9b09655},
issn = {15205126},
year = {2020},
date = {2020-01-01},
journal = {Journal of the American Chemical Society},
volume = {142},
number = {5},
pages = {2120--2124},
abstract = {Glycoside hydrolases and phosphorylases are two major classes of enzymes responsible for the cleavage of glycosidic bonds. Here we show that two GH84 O-GlcNAcase enzymes can be converted to efficient phosphorylases by a single point mutation. Noteworthy, the mutated enzymes are over 10-fold more active than naturally occurring glucosaminide phosphorylases. We rationalize this novel transformation using molecular dynamics and QM/MM metadynamics methods, showing that the mutation changes the electrostatic potential at the active site and reduces the energy barrier for phosphorolysis by 10 kcaltextperiodcenteredmol-1. In addition, the simulations unambiguously reveal the nature of the intermediate as a glucose oxazolinium ion, clarifying the debate on the nature of such a reaction intermediate in glycoside hydrolases operating via substrate-assisted catalysis.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Glycoside hydrolases and phosphorylases are two major classes of enzymes responsible for the cleavage of glycosidic bonds. Here we show that two GH84 O-GlcNAcase enzymes can be converted to efficient phosphorylases by a single point mutation. Noteworthy, the mutated enzymes are over 10-fold more active than naturally occurring glucosaminide phosphorylases. We rationalize this novel transformation using molecular dynamics and QM/MM metadynamics methods, showing that the mutation changes the electrostatic potential at the active site and reduces the energy barrier for phosphorolysis by 10 kcaltextperiodcenteredmol-1. In addition, the simulations unambiguously reveal the nature of the intermediate as a glucose oxazolinium ion, clarifying the debate on the nature of such a reaction intermediate in glycoside hydrolases operating via substrate-assisted catalysis.
Visnapuu, Triinu; Teze, David; Kjeldsen, Christian; Lie, Aleksander; Duus, Jens Øllgaard; André-Miral, Corinne; Pedersen, Lars Haastrup; Stougaard, Peter; Svensson, Birte
Identification and characterization of a β-n-acetylhexosaminidase with a biosynthetic activity from the marine bacterium paraglaciecola hydrolytica S66T Article de journal
Dans: International Journal of Molecular Sciences, vol. 21, no. 2, 2020, ISSN: 14220067.
@article{Visnapuu2020,
title = {Identification and characterization of a β-n-acetylhexosaminidase with a biosynthetic activity from the marine bacterium paraglaciecola hydrolytica S66T},
author = {Triinu Visnapuu and David Teze and Christian Kjeldsen and Aleksander Lie and Jens Øllgaard Duus and Corinne André-Miral and Lars Haastrup Pedersen and Peter Stougaard and Birte Svensson},
doi = {10.3390/ijms21020417},
issn = {14220067},
year = {2020},
date = {2020-01-01},
journal = {International Journal of Molecular Sciences},
volume = {21},
number = {2},
publisher = {MDPI AG},
abstract = {β-N-Acetylhexosaminidases are glycoside hydrolases (GHs) acting on N-acetylated carbohydrates and glycoproteins with the release of N-acetylhexosamines. Members of the family GH20 have been reported to catalyze the transfer of N-acetylglucosamine (GlcNAc) to an acceptor, i.e., the reverse of hydrolysis, thus representing an alternative to chemical oligosaccharide synthesis. Two putative GH20 β-N-acetylhexosaminidases, PhNah20A and PhNah20B, encoded by the marine bacterium Paraglaciecola hydrolytica S66T, are distantly related to previously characterized enzymes. Remarkably, PhNah20A was located by phylogenetic analysis outside clusters of other studied β-N-acetylhexosaminidases, in a unique position between bacterial and eukaryotic enzymes. We successfully produced recombinant PhNah20A showing optimum activity at pH 6.0 and 50◦C, hydrolysis of GlcNAc β-1,4 and β-1,3 linkages in chitobiose (GlcNAc)2 and GlcNAc-1,3-β-Gal-1,4-β-Glc (LNT2), a human milk oligosaccharide core structure. The kinetic parameters of PhNah20A for p-nitrophenyl-GlcNAc and p-nitrophenyl-GalNAc were highly similar: kcat /KM being 341 and 344 mM−1 s−1, respectively. PhNah20A was unstable in dilute solution, but retained full activity in the presence of 0.5% bovine serum albumin (BSA). PhNah20A catalyzed the formation of LNT2, the non-reducing trisaccharide β-Gal-1,4-β-Glc-1,1-β-GlcNAc, and in low amounts the β-1,2-or β-1,3-linked trisaccharide β-Gal-1,4(β-GlcNAc)-1,x-Glc by a transglycosylation of lactose using 2-methyl-(1,2-dideoxy-α-d-glucopyrano)-oxazoline (NAG-oxazoline) as the donor. PhNah20A is the first characterized member of a distinct subgroup within GH20 β-N-acetylhexosaminidases.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
β-N-Acetylhexosaminidases are glycoside hydrolases (GHs) acting on N-acetylated carbohydrates and glycoproteins with the release of N-acetylhexosamines. Members of the family GH20 have been reported to catalyze the transfer of N-acetylglucosamine (GlcNAc) to an acceptor, i.e., the reverse of hydrolysis, thus representing an alternative to chemical oligosaccharide synthesis. Two putative GH20 β-N-acetylhexosaminidases, PhNah20A and PhNah20B, encoded by the marine bacterium Paraglaciecola hydrolytica S66T, are distantly related to previously characterized enzymes. Remarkably, PhNah20A was located by phylogenetic analysis outside clusters of other studied β-N-acetylhexosaminidases, in a unique position between bacterial and eukaryotic enzymes. We successfully produced recombinant PhNah20A showing optimum activity at pH 6.0 and 50◦C, hydrolysis of GlcNAc β-1,4 and β-1,3 linkages in chitobiose (GlcNAc)2 and GlcNAc-1,3-β-Gal-1,4-β-Glc (LNT2), a human milk oligosaccharide core structure. The kinetic parameters of PhNah20A for p-nitrophenyl-GlcNAc and p-nitrophenyl-GalNAc were highly similar: kcat /KM being 341 and 344 mM−1 s−1, respectively. PhNah20A was unstable in dilute solution, but retained full activity in the presence of 0.5% bovine serum albumin (BSA). PhNah20A catalyzed the formation of LNT2, the non-reducing trisaccharide β-Gal-1,4-β-Glc-1,1-β-GlcNAc, and in low amounts the β-1,2-or β-1,3-linked trisaccharide β-Gal-1,4(β-GlcNAc)-1,x-Glc by a transglycosylation of lactose using 2-methyl-(1,2-dideoxy-α-d-glucopyrano)-oxazoline (NAG-oxazoline) as the donor. PhNah20A is the first characterized member of a distinct subgroup within GH20 β-N-acetylhexosaminidases.
Arbo, Bruno Dutra; André-Miral, Corinne; Nasre-Nasser, Raif Gregorio; Schimith, Lúcia Emanueli; Santos, Michele Goulart; Costa-Silva, Dennis; Muccillo-Baisch, Ana Luiza; Hort, Mariana Appel
Resveratrol Derivatives as Potential Treatments for Alzheimer’s and Parkinson’s Disease Article de journal
Dans: Frontiers in Aging Neuroscience, vol. 12, p. 103, 2020, ISSN: 1663-4365.
@article{10.3389/fnagi.2020.00103,
title = {Resveratrol Derivatives as Potential Treatments for Alzheimer’s and Parkinson’s Disease},
author = {Bruno Dutra Arbo and Corinne André-Miral and Raif Gregorio Nasre-Nasser and Lúcia Emanueli Schimith and Michele Goulart Santos and Dennis Costa-Silva and Ana Luiza Muccillo-Baisch and Mariana Appel Hort},
url = {https://www.frontiersin.org/article/10.3389/fnagi.2020.00103},
doi = {10.3389/fnagi.2020.00103},
issn = {1663-4365},
year = {2020},
date = {2020-01-01},
urldate = {2020-01-01},
journal = {Frontiers in Aging Neuroscience},
volume = {12},
pages = {103},
abstract = {Neurodegenerative diseases are characterized by the progressive loss of neurons in different regions of the nervous system. Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the two most prevalent neurodegenerative diseases, and the symptoms associated with these pathologies are closely related to the regions that are most affected by the process of neurodegeneration. Despite their high prevalence, currently, there is no cure or disease-modifying drugs for the treatment of these conditions. In the last decades, due to the need for the development of new treatments for neurodegenerative diseases, several authors have investigated the neuroprotective actions of naturally occurring molecules, such as resveratrol. Resveratrol is a stilbene found in several plants, including grapes, blueberries, raspberries, and peanuts. Studies have shown that resveratrol presents neuroprotective actions in experimental models of AD and PD, however, its clinical application is limited due to its rapid metabolism and low bioavailability. In this context, studies have proposed that structural changes in the resveratrol molecule, including glycosylation, alkylation, halogenation, hydroxylation, methylation, and prenylation could lead to the development of derivatives with enhanced bioavailability and pharmacological activity. Therefore, this review article aims to discuss how resveratrol derivatives could represent viable molecules in the search for new drugs for the treatment of AD and PD.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Neurodegenerative diseases are characterized by the progressive loss of neurons in different regions of the nervous system. Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the two most prevalent neurodegenerative diseases, and the symptoms associated with these pathologies are closely related to the regions that are most affected by the process of neurodegeneration. Despite their high prevalence, currently, there is no cure or disease-modifying drugs for the treatment of these conditions. In the last decades, due to the need for the development of new treatments for neurodegenerative diseases, several authors have investigated the neuroprotective actions of naturally occurring molecules, such as resveratrol. Resveratrol is a stilbene found in several plants, including grapes, blueberries, raspberries, and peanuts. Studies have shown that resveratrol presents neuroprotective actions in experimental models of AD and PD, however, its clinical application is limited due to its rapid metabolism and low bioavailability. In this context, studies have proposed that structural changes in the resveratrol molecule, including glycosylation, alkylation, halogenation, hydroxylation, methylation, and prenylation could lead to the development of derivatives with enhanced bioavailability and pharmacological activity. Therefore, this review article aims to discuss how resveratrol derivatives could represent viable molecules in the search for new drugs for the treatment of AD and PD.
1 publication
André-Miral, Corinne; Koné, Fankroma Mt; Solleux, Claude; Grandjean, Cyrille; Dion, Michel; Tran, Vinh; Tellier, Charles
De novo design of a trans-β-N-acetylglucosaminidase activity from a GH1 β-glycosidase by mechanism engineering Article de journal
Dans: Glycobiology, vol. 25, no. 4, p. 394–402, 2015, ISSN: 14602423.
@article{Andre-Miral2015,
title = {De novo design of a trans-β-N-acetylglucosaminidase activity from a GH1 β-glycosidase by mechanism engineering},
author = {Corinne André-Miral and Fankroma Mt Koné and Claude Solleux and Cyrille Grandjean and Michel Dion and Vinh Tran and Charles Tellier},
doi = {10.1093/glycob/cwu121},
issn = {14602423},
year = {2015},
date = {2015-01-01},
journal = {Glycobiology},
volume = {25},
number = {4},
pages = {394--402},
abstract = {Glycoside hydrolases are particularly abundant in all areas of metabolism as they are involved in the degradation of natural polysaccharides and glycoconjugates. These enzymes are classified into 133 families (CAZy server, http://www.cazy.org) in which members of each family have a similar structure and catalytic mechanism. In order to understand better the structure/function relationships of these enzymes and their evolution and to develop new robust evolved glycosidases, we undertook to convert a Family 1 thermostable β-glycosidase into an exo-β-N-acetylglucosaminidase. This latter activity is totally absent in Family 1, while natural β-hexosaminidases belong to CAZy Families 3, 20 and 84. Using molecular modeling, we first showed that the docking of N-acetyl-d-glucosamine in the subsite -1 of the β-glycosidase from Thermus thermophilus (TtβGly) suggested several steric conflicts with active site amino-acids (N163, E338) induced by the N-acetyl group. Both N163A and N163D-E338G mutations induced significant N-acetylglucosaminidase activity in TtβGly. The double mutant N163D-E338G was also active on the bicyclic oxazoline substrate, suggesting that this mutated enzyme uses a catalytic mechanism involving a substrate-assisted catalysis with a noncovalent oxazoline intermediate, similar to the N-acetylglucosaminidases from Families 20 and 84. Furthermore, a very efficient trans-N-acetylglucosaminidase activity was observed when the double mutant was incubated in the presence of NAG-oxazoline as a donor and N-methyl-O-benzyl-N-(β-d-glucopyranosyl)-hydroxylamine as an acceptor. More generally, this work demonstrates that it is possible to exchange the specificities and catalytic mechanisms with minimal changes between phylogenetically distant protein structures.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Glycoside hydrolases are particularly abundant in all areas of metabolism as they are involved in the degradation of natural polysaccharides and glycoconjugates. These enzymes are classified into 133 families (CAZy server, http://www.cazy.org) in which members of each family have a similar structure and catalytic mechanism. In order to understand better the structure/function relationships of these enzymes and their evolution and to develop new robust evolved glycosidases, we undertook to convert a Family 1 thermostable β-glycosidase into an exo-β-N-acetylglucosaminidase. This latter activity is totally absent in Family 1, while natural β-hexosaminidases belong to CAZy Families 3, 20 and 84. Using molecular modeling, we first showed that the docking of N-acetyl-d-glucosamine in the subsite -1 of the β-glycosidase from Thermus thermophilus (TtβGly) suggested several steric conflicts with active site amino-acids (N163, E338) induced by the N-acetyl group. Both N163A and N163D-E338G mutations induced significant N-acetylglucosaminidase activity in TtβGly. The double mutant N163D-E338G was also active on the bicyclic oxazoline substrate, suggesting that this mutated enzyme uses a catalytic mechanism involving a substrate-assisted catalysis with a noncovalent oxazoline intermediate, similar to the N-acetylglucosaminidases from Families 20 and 84. Furthermore, a very efficient trans-N-acetylglucosaminidase activity was observed when the double mutant was incubated in the presence of NAG-oxazoline as a donor and N-methyl-O-benzyl-N-(β-d-glucopyranosyl)-hydroxylamine as an acceptor. More generally, this work demonstrates that it is possible to exchange the specificities and catalytic mechanisms with minimal changes between phylogenetically distant protein structures.