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Exenatide induces frataxin expression and improves mitochondrial function in Friedreich ataxia.

Identifieur interne : 000134 ( Main/Exploration ); précédent : 000133; suivant : 000135

Exenatide induces frataxin expression and improves mitochondrial function in Friedreich ataxia.

Auteurs : Mariana Igoillo-Esteve ; Ana F. Oliveira ; Cristina Cosentino ; Federica Fantuzzi [Italie] ; Céline Demarez ; Sanna Toivonen ; Amélie Hu [Belgique] ; Satyan Chintawar [Belgique] ; Miguel Lopes ; Nathalie Pachera ; Ying Cai ; Baroj Abdulkarim ; Myriam Rai [Belgique] ; Lorella Marselli [Italie] ; Piero Marchetti [Italie] ; Mohammad Tariq [Italie] ; Jean-Christophe Jonas [Belgique] ; Marina Boscolo [Belgique] ; Massimo Pandolfo [Belgique] ; Décio L. Eizirik [États-Unis] ; Miriam Cnop [Belgique]

Source :

RBID : pubmed:31877117

Descripteurs français

English descriptors

Abstract

Friedreich ataxia is an autosomal recessive neurodegenerative disease associated with a high diabetes prevalence. No treatment is available to prevent or delay disease progression. Friedreich ataxia is caused by intronic GAA trinucleotide repeat expansions in the frataxin-encoding FXN gene that reduce frataxin expression, impair iron-sulfur cluster biogenesis, cause oxidative stress, and result in mitochondrial dysfunction and apoptosis. Here we examined the metabolic, neuroprotective, and frataxin-inducing effects of glucagon-like peptide-1 (GLP-1) analogs in in vivo and in vitro models and in patients with Friedreich ataxia. The GLP-1 analog exenatide improved glucose homeostasis of frataxin-deficient mice through enhanced insulin content and secretion in pancreatic β cells. Exenatide induced frataxin and iron-sulfur cluster-containing proteins in β cells and brain and was protective to sensory neurons in dorsal root ganglia. GLP-1 analogs also induced frataxin expression, reduced oxidative stress, and improved mitochondrial function in Friedreich ataxia patients' induced pluripotent stem cell-derived β cells and sensory neurons. The frataxin-inducing effect of exenatide was confirmed in a pilot trial in Friedreich ataxia patients, showing modest frataxin induction in platelets over a 5-week treatment course. Taken together, GLP-1 analogs improve mitochondrial function in frataxin-deficient cells and induce frataxin expression. Our findings identify incretin receptors as a therapeutic target in Friedreich ataxia.

DOI: 10.1172/jci.insight.134221
PubMed: 31877117
PubMed Central: PMC7098728


Affiliations:


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Le document en format XML

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<name sortKey="Cai, Ying" sort="Cai, Ying" uniqKey="Cai Y" first="Ying" last="Cai">Ying Cai</name>
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<name sortKey="Abdulkarim, Baroj" sort="Abdulkarim, Baroj" uniqKey="Abdulkarim B" first="Baroj" last="Abdulkarim">Baroj Abdulkarim</name>
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<name sortKey="Boscolo, Marina" sort="Boscolo, Marina" uniqKey="Boscolo M" first="Marina" last="Boscolo">Marina Boscolo</name>
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<name sortKey="Pandolfo, Massimo" sort="Pandolfo, Massimo" uniqKey="Pandolfo M" first="Massimo" last="Pandolfo">Massimo Pandolfo</name>
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<name sortKey="Eizirik, Decio L" sort="Eizirik, Decio L" uniqKey="Eizirik D" first="Décio L" last="Eizirik">Décio L. Eizirik</name>
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<nlm:affiliation>Indiana Biosciences Research Institute, Indianapolis, Indiana, USA.</nlm:affiliation>
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<name sortKey="Cnop, Miriam" sort="Cnop, Miriam" uniqKey="Cnop M" first="Miriam" last="Cnop">Miriam Cnop</name>
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<title xml:lang="en">Exenatide induces frataxin expression and improves mitochondrial function in Friedreich ataxia.</title>
<author>
<name sortKey="Igoillo Esteve, Mariana" sort="Igoillo Esteve, Mariana" uniqKey="Igoillo Esteve M" first="Mariana" last="Igoillo-Esteve">Mariana Igoillo-Esteve</name>
<affiliation>
<nlm:affiliation>ULB Center for Diabetes Research and.</nlm:affiliation>
<wicri:noCountry code="no comma">ULB Center for Diabetes Research and.</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Oliveira, Ana F" sort="Oliveira, Ana F" uniqKey="Oliveira A" first="Ana F" last="Oliveira">Ana F. Oliveira</name>
<affiliation>
<nlm:affiliation>ULB Center for Diabetes Research and.</nlm:affiliation>
<wicri:noCountry code="no comma">ULB Center for Diabetes Research and.</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Cosentino, Cristina" sort="Cosentino, Cristina" uniqKey="Cosentino C" first="Cristina" last="Cosentino">Cristina Cosentino</name>
<affiliation>
<nlm:affiliation>ULB Center for Diabetes Research and.</nlm:affiliation>
<wicri:noCountry code="no comma">ULB Center for Diabetes Research and.</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Fantuzzi, Federica" sort="Fantuzzi, Federica" uniqKey="Fantuzzi F" first="Federica" last="Fantuzzi">Federica Fantuzzi</name>
<affiliation>
<nlm:affiliation>ULB Center for Diabetes Research and.</nlm:affiliation>
<wicri:noCountry code="no comma">ULB Center for Diabetes Research and.</wicri:noCountry>
</affiliation>
<affiliation wicri:level="1">
<nlm:affiliation>Endocrinology and Metabolism, Department of Medicine and Surgery, University of Parma, Parma, Italy.</nlm:affiliation>
<country xml:lang="fr">Italie</country>
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<name sortKey="Demarez, Celine" sort="Demarez, Celine" uniqKey="Demarez C" first="Céline" last="Demarez">Céline Demarez</name>
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<nlm:affiliation>ULB Center for Diabetes Research and.</nlm:affiliation>
<wicri:noCountry code="no comma">ULB Center for Diabetes Research and.</wicri:noCountry>
</affiliation>
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<name sortKey="Toivonen, Sanna" sort="Toivonen, Sanna" uniqKey="Toivonen S" first="Sanna" last="Toivonen">Sanna Toivonen</name>
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<nlm:affiliation>ULB Center for Diabetes Research and.</nlm:affiliation>
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<name sortKey="Hu, Amelie" sort="Hu, Amelie" uniqKey="Hu A" first="Amélie" last="Hu">Amélie Hu</name>
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<name sortKey="Chintawar, Satyan" sort="Chintawar, Satyan" uniqKey="Chintawar S" first="Satyan" last="Chintawar">Satyan Chintawar</name>
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<nlm:affiliation>Laboratory of Experimental Neurology, Université Libre de Bruxelles, Brussels, Belgium.</nlm:affiliation>
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<name sortKey="Lopes, Miguel" sort="Lopes, Miguel" uniqKey="Lopes M" first="Miguel" last="Lopes">Miguel Lopes</name>
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</affiliation>
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<name sortKey="Pachera, Nathalie" sort="Pachera, Nathalie" uniqKey="Pachera N" first="Nathalie" last="Pachera">Nathalie Pachera</name>
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<name sortKey="Cai, Ying" sort="Cai, Ying" uniqKey="Cai Y" first="Ying" last="Cai">Ying Cai</name>
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<nlm:affiliation>ULB Center for Diabetes Research and.</nlm:affiliation>
<wicri:noCountry code="no comma">ULB Center for Diabetes Research and.</wicri:noCountry>
</affiliation>
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<author>
<name sortKey="Abdulkarim, Baroj" sort="Abdulkarim, Baroj" uniqKey="Abdulkarim B" first="Baroj" last="Abdulkarim">Baroj Abdulkarim</name>
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<nlm:affiliation>ULB Center for Diabetes Research and.</nlm:affiliation>
<wicri:noCountry code="no comma">ULB Center for Diabetes Research and.</wicri:noCountry>
</affiliation>
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<name sortKey="Rai, Myriam" sort="Rai, Myriam" uniqKey="Rai M" first="Myriam" last="Rai">Myriam Rai</name>
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<name sortKey="Marselli, Lorella" sort="Marselli, Lorella" uniqKey="Marselli L" first="Lorella" last="Marselli">Lorella Marselli</name>
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<nlm:affiliation>Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.</nlm:affiliation>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Department of Clinical and Experimental Medicine, University of Pisa, Pisa</wicri:regionArea>
<placeName>
<settlement type="city">Pise</settlement>
<region nuts="2">Toscane</region>
</placeName>
<orgName type="university">Université de Pise</orgName>
</affiliation>
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<author>
<name sortKey="Marchetti, Piero" sort="Marchetti, Piero" uniqKey="Marchetti P" first="Piero" last="Marchetti">Piero Marchetti</name>
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<nlm:affiliation>Endocrinology and Metabolism, Department of Medicine and Surgery, University of Parma, Parma, Italy.</nlm:affiliation>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Endocrinology and Metabolism, Department of Medicine and Surgery, University of Parma, Parma</wicri:regionArea>
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<name sortKey="Tariq, Mohammad" sort="Tariq, Mohammad" uniqKey="Tariq M" first="Mohammad" last="Tariq">Mohammad Tariq</name>
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<nlm:affiliation>Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.</nlm:affiliation>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Department of Clinical and Experimental Medicine, University of Pisa, Pisa</wicri:regionArea>
<placeName>
<settlement type="city">Pise</settlement>
<region nuts="2">Toscane</region>
</placeName>
<orgName type="university">Université de Pise</orgName>
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<name sortKey="Jonas, Jean Christophe" sort="Jonas, Jean Christophe" uniqKey="Jonas J" first="Jean-Christophe" last="Jonas">Jean-Christophe Jonas</name>
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<nlm:affiliation>Pole of Endocrinology, Diabetes and Nutrition, Institute of Experimental and Clinical Research, Université Catholique de Louvain, Brussels, Belgium.</nlm:affiliation>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea>Pole of Endocrinology, Diabetes and Nutrition, Institute of Experimental and Clinical Research, Université Catholique de Louvain, Brussels</wicri:regionArea>
<placeName>
<settlement type="city">Bruxelles</settlement>
<region nuts="2">Région de Bruxelles-Capitale</region>
</placeName>
<orgName type="university">Université catholique de Louvain</orgName>
</affiliation>
</author>
<author>
<name sortKey="Boscolo, Marina" sort="Boscolo, Marina" uniqKey="Boscolo M" first="Marina" last="Boscolo">Marina Boscolo</name>
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<nlm:affiliation>Division of Endocrinology, Erasmus Hospital, Université Libre de Bruxelles, Brussels, Belgium.</nlm:affiliation>
<country xml:lang="fr">Belgique</country>
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<orgName type="university">Université libre de Bruxelles</orgName>
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<author>
<name sortKey="Pandolfo, Massimo" sort="Pandolfo, Massimo" uniqKey="Pandolfo M" first="Massimo" last="Pandolfo">Massimo Pandolfo</name>
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<nlm:affiliation>Laboratory of Experimental Neurology, Université Libre de Bruxelles, Brussels, Belgium.</nlm:affiliation>
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<author>
<name sortKey="Eizirik, Decio L" sort="Eizirik, Decio L" uniqKey="Eizirik D" first="Décio L" last="Eizirik">Décio L. Eizirik</name>
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<nlm:affiliation>ULB Center for Diabetes Research and.</nlm:affiliation>
<wicri:noCountry code="no comma">ULB Center for Diabetes Research and.</wicri:noCountry>
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<affiliation wicri:level="2">
<nlm:affiliation>Indiana Biosciences Research Institute, Indianapolis, Indiana, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Indiana Biosciences Research Institute, Indianapolis, Indiana</wicri:regionArea>
<placeName>
<region type="state">Indiana</region>
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<author>
<name sortKey="Cnop, Miriam" sort="Cnop, Miriam" uniqKey="Cnop M" first="Miriam" last="Cnop">Miriam Cnop</name>
<affiliation>
<nlm:affiliation>ULB Center for Diabetes Research and.</nlm:affiliation>
<wicri:noCountry code="no comma">ULB Center for Diabetes Research and.</wicri:noCountry>
</affiliation>
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<nlm:affiliation>Division of Endocrinology, Erasmus Hospital, Université Libre de Bruxelles, Brussels, Belgium.</nlm:affiliation>
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<title level="j">JCI insight</title>
<idno type="eISSN">2379-3708</idno>
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<term>Adolescent (MeSH)</term>
<term>Adult (MeSH)</term>
<term>Aged (MeSH)</term>
<term>Animals (MeSH)</term>
<term>Brain (pathology)</term>
<term>Cerebellum (pathology)</term>
<term>Disease Models, Animal (MeSH)</term>
<term>Exenatide (pharmacology)</term>
<term>Exenatide (therapeutic use)</term>
<term>Female (MeSH)</term>
<term>Friedreich Ataxia (drug therapy)</term>
<term>Friedreich Ataxia (genetics)</term>
<term>Friedreich Ataxia (metabolism)</term>
<term>Ganglia, Spinal (pathology)</term>
<term>Gene Expression Regulation (drug effects)</term>
<term>Gene Knock-In Techniques (MeSH)</term>
<term>Glucagon-Like Peptide 1 (analogs & derivatives)</term>
<term>Glucagon-Like Peptide 1 (metabolism)</term>
<term>Humans (MeSH)</term>
<term>Insulin (metabolism)</term>
<term>Insulin-Secreting Cells (metabolism)</term>
<term>Iron (metabolism)</term>
<term>Iron-Binding Proteins (genetics)</term>
<term>Iron-Binding Proteins (metabolism)</term>
<term>Male (MeSH)</term>
<term>Mice (MeSH)</term>
<term>Mice, Knockout (MeSH)</term>
<term>Middle Aged (MeSH)</term>
<term>Mitochondria (metabolism)</term>
<term>Oxidative Stress (MeSH)</term>
<term>Reactive Oxygen Species (metabolism)</term>
<term>Trinucleotide Repeat Expansion (MeSH)</term>
<term>Young Adult (MeSH)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr">
<term>Adolescent (MeSH)</term>
<term>Adulte (MeSH)</term>
<term>Adulte d'âge moyen (MeSH)</term>
<term>Animaux (MeSH)</term>
<term>Ataxie de Friedreich (génétique)</term>
<term>Ataxie de Friedreich (métabolisme)</term>
<term>Ataxie de Friedreich (traitement médicamenteux)</term>
<term>Cellules à insuline (métabolisme)</term>
<term>Cervelet (anatomopathologie)</term>
<term>Encéphale (anatomopathologie)</term>
<term>Espèces réactives de l'oxygène (métabolisme)</term>
<term>Expansion de trinucléotide répété (MeSH)</term>
<term>Exénatide (pharmacologie)</term>
<term>Exénatide (usage thérapeutique)</term>
<term>Femelle (MeSH)</term>
<term>Fer (métabolisme)</term>
<term>Ganglions sensitifs des nerfs spinaux (anatomopathologie)</term>
<term>Glucagon-like peptide 1 (analogues et dérivés)</term>
<term>Glucagon-like peptide 1 (métabolisme)</term>
<term>Humains (MeSH)</term>
<term>Insuline (métabolisme)</term>
<term>Jeune adulte (MeSH)</term>
<term>Mitochondries (métabolisme)</term>
<term>Modèles animaux de maladie humaine (MeSH)</term>
<term>Mâle (MeSH)</term>
<term>Protéines de liaison au fer (génétique)</term>
<term>Protéines de liaison au fer (métabolisme)</term>
<term>Régulation de l'expression des gènes (effets des médicaments et des substances chimiques)</term>
<term>Souris (MeSH)</term>
<term>Souris knockout (MeSH)</term>
<term>Stress oxydatif (MeSH)</term>
<term>Sujet âgé (MeSH)</term>
<term>Techniques de knock-in de gènes (MeSH)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="analogs & derivatives" xml:lang="en">
<term>Glucagon-Like Peptide 1</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en">
<term>Iron-Binding Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en">
<term>Glucagon-Like Peptide 1</term>
<term>Insulin</term>
<term>Iron</term>
<term>Iron-Binding Proteins</term>
<term>Reactive Oxygen Species</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en">
<term>Exenatide</term>
</keywords>
<keywords scheme="MESH" qualifier="analogues et dérivés" xml:lang="fr">
<term>Glucagon-like peptide 1</term>
</keywords>
<keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr">
<term>Cervelet</term>
<term>Encéphale</term>
<term>Ganglions sensitifs des nerfs spinaux</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en">
<term>Gene Expression Regulation</term>
</keywords>
<keywords scheme="MESH" qualifier="drug therapy" xml:lang="en">
<term>Friedreich Ataxia</term>
</keywords>
<keywords scheme="MESH" qualifier="effets des médicaments et des substances chimiques" xml:lang="fr">
<term>Régulation de l'expression des gènes</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en">
<term>Friedreich Ataxia</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr">
<term>Ataxie de Friedreich</term>
<term>Protéines de liaison au fer</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en">
<term>Friedreich Ataxia</term>
<term>Insulin-Secreting Cells</term>
<term>Mitochondria</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr">
<term>Ataxie de Friedreich</term>
<term>Cellules à insuline</term>
<term>Espèces réactives de l'oxygène</term>
<term>Fer</term>
<term>Glucagon-like peptide 1</term>
<term>Insuline</term>
<term>Mitochondries</term>
<term>Protéines de liaison au fer</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en">
<term>Brain</term>
<term>Cerebellum</term>
<term>Ganglia, Spinal</term>
</keywords>
<keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr">
<term>Exénatide</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en">
<term>Exenatide</term>
</keywords>
<keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr">
<term>Ataxie de Friedreich</term>
</keywords>
<keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr">
<term>Exénatide</term>
</keywords>
<keywords scheme="MESH" xml:lang="en">
<term>Adolescent</term>
<term>Adult</term>
<term>Aged</term>
<term>Animals</term>
<term>Disease Models, Animal</term>
<term>Female</term>
<term>Gene Knock-In Techniques</term>
<term>Humans</term>
<term>Male</term>
<term>Mice</term>
<term>Mice, Knockout</term>
<term>Middle Aged</term>
<term>Oxidative Stress</term>
<term>Trinucleotide Repeat Expansion</term>
<term>Young Adult</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr">
<term>Adolescent</term>
<term>Adulte</term>
<term>Adulte d'âge moyen</term>
<term>Animaux</term>
<term>Expansion de trinucléotide répété</term>
<term>Femelle</term>
<term>Humains</term>
<term>Jeune adulte</term>
<term>Modèles animaux de maladie humaine</term>
<term>Mâle</term>
<term>Souris</term>
<term>Souris knockout</term>
<term>Stress oxydatif</term>
<term>Sujet âgé</term>
<term>Techniques de knock-in de gènes</term>
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<front>
<div type="abstract" xml:lang="en">Friedreich ataxia is an autosomal recessive neurodegenerative disease associated with a high diabetes prevalence. No treatment is available to prevent or delay disease progression. Friedreich ataxia is caused by intronic GAA trinucleotide repeat expansions in the frataxin-encoding FXN gene that reduce frataxin expression, impair iron-sulfur cluster biogenesis, cause oxidative stress, and result in mitochondrial dysfunction and apoptosis. Here we examined the metabolic, neuroprotective, and frataxin-inducing effects of glucagon-like peptide-1 (GLP-1) analogs in in vivo and in vitro models and in patients with Friedreich ataxia. The GLP-1 analog exenatide improved glucose homeostasis of frataxin-deficient mice through enhanced insulin content and secretion in pancreatic β cells. Exenatide induced frataxin and iron-sulfur cluster-containing proteins in β cells and brain and was protective to sensory neurons in dorsal root ganglia. GLP-1 analogs also induced frataxin expression, reduced oxidative stress, and improved mitochondrial function in Friedreich ataxia patients' induced pluripotent stem cell-derived β cells and sensory neurons. The frataxin-inducing effect of exenatide was confirmed in a pilot trial in Friedreich ataxia patients, showing modest frataxin induction in platelets over a 5-week treatment course. Taken together, GLP-1 analogs improve mitochondrial function in frataxin-deficient cells and induce frataxin expression. Our findings identify incretin receptors as a therapeutic target in Friedreich ataxia.</div>
</front>
</TEI>
<pubmed>
<MedlineCitation Status="MEDLINE" Owner="NLM">
<PMID Version="1">31877117</PMID>
<DateCompleted>
<Year>2020</Year>
<Month>11</Month>
<Day>20</Day>
</DateCompleted>
<DateRevised>
<Year>2020</Year>
<Month>11</Month>
<Day>20</Day>
</DateRevised>
<Article PubModel="Electronic">
<Journal>
<ISSN IssnType="Electronic">2379-3708</ISSN>
<JournalIssue CitedMedium="Internet">
<Volume>5</Volume>
<Issue>2</Issue>
<PubDate>
<Year>2020</Year>
<Month>01</Month>
<Day>30</Day>
</PubDate>
</JournalIssue>
<Title>JCI insight</Title>
<ISOAbbreviation>JCI Insight</ISOAbbreviation>
</Journal>
<ArticleTitle>Exenatide induces frataxin expression and improves mitochondrial function in Friedreich ataxia.</ArticleTitle>
<ELocationID EIdType="doi" ValidYN="Y">10.1172/jci.insight.134221</ELocationID>
<ELocationID EIdType="pii" ValidYN="Y">134221</ELocationID>
<Abstract>
<AbstractText>Friedreich ataxia is an autosomal recessive neurodegenerative disease associated with a high diabetes prevalence. No treatment is available to prevent or delay disease progression. Friedreich ataxia is caused by intronic GAA trinucleotide repeat expansions in the frataxin-encoding FXN gene that reduce frataxin expression, impair iron-sulfur cluster biogenesis, cause oxidative stress, and result in mitochondrial dysfunction and apoptosis. Here we examined the metabolic, neuroprotective, and frataxin-inducing effects of glucagon-like peptide-1 (GLP-1) analogs in in vivo and in vitro models and in patients with Friedreich ataxia. The GLP-1 analog exenatide improved glucose homeostasis of frataxin-deficient mice through enhanced insulin content and secretion in pancreatic β cells. Exenatide induced frataxin and iron-sulfur cluster-containing proteins in β cells and brain and was protective to sensory neurons in dorsal root ganglia. GLP-1 analogs also induced frataxin expression, reduced oxidative stress, and improved mitochondrial function in Friedreich ataxia patients' induced pluripotent stem cell-derived β cells and sensory neurons. The frataxin-inducing effect of exenatide was confirmed in a pilot trial in Friedreich ataxia patients, showing modest frataxin induction in platelets over a 5-week treatment course. Taken together, GLP-1 analogs improve mitochondrial function in frataxin-deficient cells and induce frataxin expression. Our findings identify incretin receptors as a therapeutic target in Friedreich ataxia.</AbstractText>
</Abstract>
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<Author ValidYN="Y">
<LastName>Igoillo-Esteve</LastName>
<ForeName>Mariana</ForeName>
<Initials>M</Initials>
<AffiliationInfo>
<Affiliation>ULB Center for Diabetes Research and.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Oliveira</LastName>
<ForeName>Ana F</ForeName>
<Initials>AF</Initials>
<AffiliationInfo>
<Affiliation>ULB Center for Diabetes Research and.</Affiliation>
</AffiliationInfo>
</Author>
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<LastName>Cosentino</LastName>
<ForeName>Cristina</ForeName>
<Initials>C</Initials>
<AffiliationInfo>
<Affiliation>ULB Center for Diabetes Research and.</Affiliation>
</AffiliationInfo>
</Author>
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<LastName>Fantuzzi</LastName>
<ForeName>Federica</ForeName>
<Initials>F</Initials>
<AffiliationInfo>
<Affiliation>ULB Center for Diabetes Research and.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>Endocrinology and Metabolism, Department of Medicine and Surgery, University of Parma, Parma, Italy.</Affiliation>
</AffiliationInfo>
</Author>
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<LastName>Demarez</LastName>
<ForeName>Céline</ForeName>
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<AffiliationInfo>
<Affiliation>ULB Center for Diabetes Research and.</Affiliation>
</AffiliationInfo>
</Author>
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<LastName>Toivonen</LastName>
<ForeName>Sanna</ForeName>
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<Affiliation>ULB Center for Diabetes Research and.</Affiliation>
</AffiliationInfo>
</Author>
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<LastName>Hu</LastName>
<ForeName>Amélie</ForeName>
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<ForeName>Satyan</ForeName>
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</AffiliationInfo>
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<ForeName>Nathalie</ForeName>
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</AffiliationInfo>
</Author>
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<LastName>Cai</LastName>
<ForeName>Ying</ForeName>
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</AffiliationInfo>
</Author>
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<LastName>Abdulkarim</LastName>
<ForeName>Baroj</ForeName>
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</AffiliationInfo>
</Author>
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<LastName>Rai</LastName>
<ForeName>Myriam</ForeName>
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</AffiliationInfo>
</Author>
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<LastName>Marselli</LastName>
<ForeName>Lorella</ForeName>
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<Affiliation>Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.</Affiliation>
</AffiliationInfo>
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<LastName>Marchetti</LastName>
<ForeName>Piero</ForeName>
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<Affiliation>Endocrinology and Metabolism, Department of Medicine and Surgery, University of Parma, Parma, Italy.</Affiliation>
</AffiliationInfo>
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<LastName>Tariq</LastName>
<ForeName>Mohammad</ForeName>
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<Affiliation>Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.</Affiliation>
</AffiliationInfo>
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<LastName>Jonas</LastName>
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<AffiliationInfo>
<Affiliation>Pole of Endocrinology, Diabetes and Nutrition, Institute of Experimental and Clinical Research, Université Catholique de Louvain, Brussels, Belgium.</Affiliation>
</AffiliationInfo>
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<LastName>Boscolo</LastName>
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<Affiliation>Division of Endocrinology, Erasmus Hospital, Université Libre de Bruxelles, Brussels, Belgium.</Affiliation>
</AffiliationInfo>
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</AffiliationInfo>
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</AffiliationInfo>
<AffiliationInfo>
<Affiliation>Indiana Biosciences Research Institute, Indianapolis, Indiana, USA.</Affiliation>
</AffiliationInfo>
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<ForeName>Miriam</ForeName>
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<Affiliation>ULB Center for Diabetes Research and.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>Division of Endocrinology, Erasmus Hospital, Université Libre de Bruxelles, Brussels, Belgium.</Affiliation>
</AffiliationInfo>
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<DescriptorName UI="D005786" MajorTopicYN="N">Gene Expression Regulation</DescriptorName>
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<MeshHeading>
<DescriptorName UI="D055879" MajorTopicYN="N">Gene Knock-In Techniques</DescriptorName>
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   |texte=   Exenatide induces frataxin expression and improves mitochondrial function in Friedreich ataxia.
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