Mitochondria as pharmacological targets in Down syndrome.
Identifieur interne : 000799 ( Main/Exploration ); précédent : 000798; suivant : 000800Mitochondria as pharmacological targets in Down syndrome.
Auteurs : Daniela Valenti [Italie] ; Nady Braidy [Australie] ; Domenico De Rasmo [Italie] ; Anna Signorile [Italie] ; Leonardo Rossi [Italie] ; A G Atanasov [Autriche] ; Mariateresa Volpicella [Italie] ; Alexandra Henrion-Caude [France] ; S M Nabavi [Iran] ; R A Vacca [Italie]Source :
- Free radical biology & medicine [ 1873-4596 ] ; 2017.
Abstract
Mitochondria play a pivotal role in cellular energy-generating processes and are considered master regulators of cell life and death fate. Mitochondrial function integrates signalling networks in several metabolic pathways controlling neurogenesis and neuroplasticity. Indeed, dysfunctional mitochondria and mitochondrial-dependent activation of intracellular stress cascades are critical initiating events in many human neurodegenerative or neurodevelopmental diseases including Down syndrome (DS). It is well established that trisomy of human chromosome 21 can cause DS. DS is associated with neurodevelopmental delay, intellectual disability and early neurodegeneration. Recently, molecular mechanisms responsible for mitochondrial damage and energy deficits have been identified and characterized in several DS-derived human cells and animal models of DS. Therefore, therapeutic strategies targeting mitochondria could have great potential for new treatment regimens in DS. The purpose of this review is to highlight recent studies concerning mitochondrial impairment in DS, focusing on alterations of the molecular pathways controlling mitochondrial function. We will also discuss the effects and molecular mechanisms of naturally occurring and chemically synthetized drugs that exert neuroprotective effects through modulation of mitochondrial function and attenuation of oxidative stress. These compounds might represent novel therapeutic tools for the modulation of energy deficits in DS.
DOI: 10.1016/j.freeradbiomed.2017.08.014
PubMed: 28838841
Affiliations:
- Australie, Autriche, France, Iran, Italie
- Toscane, Vienne (Autriche), Île-de-France
- Paris, Pise, Vienne (Autriche)
- Université Paris-Descartes, Université de Pise
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Department of Pharmacognosy, University of Vienna, 1090 Vienna, Austria; Department of Vascular Biology and Thrombosis Research, Center for Physiology and Pharmacology, Medical University of Vienna, 1090 Vienna, Austria.</nlm:affiliation><country xml:lang="fr">Autriche</country><wicri:regionArea>Institute of Genetics and Animal Breeding of the Polish Academy of Sciences, 05-552 Jastrzebiec, Poland; Department of Pharmacognosy, University of Vienna, 1090 Vienna, Austria; Department of Vascular Biology and Thrombosis Research, Center for Physiology and Pharmacology, Medical University of Vienna, 1090 Vienna</wicri:regionArea><placeName><region type="land" nuts="2">Vienne (Autriche)</region><settlement type="city">Vienne (Autriche)</settlement></placeName></affiliation></author><author><name sortKey="Volpicella, Mariateresa" sort="Volpicella, Mariateresa" uniqKey="Volpicella M" first="Mariateresa" last="Volpicella">Mariateresa Volpicella</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Bari, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Bari</wicri:regionArea><wicri:noRegion>Bari</wicri:noRegion></affiliation></author><author><name sortKey="Henrion Caude, Alexandra" sort="Henrion Caude, Alexandra" uniqKey="Henrion Caude A" first="Alexandra" last="Henrion-Caude">Alexandra Henrion-Caude</name><affiliation wicri:level="4"><nlm:affiliation>INSERM U1163, Université Paris Descartes, Sorbonne Paris Cité, Institut Imagine, GenAtlas Platform, 24 Boulevard du Montparnasse, 75015 Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INSERM U1163, Université Paris Descartes, Sorbonne Paris Cité, Institut Imagine, GenAtlas Platform, 24 Boulevard du Montparnasse, 75015 Paris</wicri:regionArea><wicri:noRegion>75015 Paris</wicri:noRegion><placeName><settlement type="city">Paris</settlement><region type="région" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName><orgName type="university">Université Paris-Descartes</orgName></affiliation></author><author><name sortKey="Nabavi, S M" sort="Nabavi, S M" uniqKey="Nabavi S" first="S M" last="Nabavi">S M Nabavi</name><affiliation wicri:level="1"><nlm:affiliation>Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.</nlm:affiliation><country xml:lang="fr">Iran</country><wicri:regionArea>Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran</wicri:regionArea><wicri:noRegion>Tehran</wicri:noRegion></affiliation></author><author><name sortKey="Vacca, R A" sort="Vacca, R A" uniqKey="Vacca R" first="R A" last="Vacca">R A Vacca</name><affiliation wicri:level="1"><nlm:affiliation>Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies, National Council of Research, Bari, Italy. 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Department of Pharmacognosy, University of Vienna, 1090 Vienna, Austria; Department of Vascular Biology and Thrombosis Research, Center for Physiology and Pharmacology, Medical University of Vienna, 1090 Vienna, Austria.</nlm:affiliation><country xml:lang="fr">Autriche</country><wicri:regionArea>Institute of Genetics and Animal Breeding of the Polish Academy of Sciences, 05-552 Jastrzebiec, Poland; Department of Pharmacognosy, University of Vienna, 1090 Vienna, Austria; Department of Vascular Biology and Thrombosis Research, Center for Physiology and Pharmacology, Medical University of Vienna, 1090 Vienna</wicri:regionArea><placeName><region type="land" nuts="2">Vienne (Autriche)</region><settlement type="city">Vienne (Autriche)</settlement></placeName></affiliation></author><author><name sortKey="Volpicella, Mariateresa" sort="Volpicella, Mariateresa" uniqKey="Volpicella M" first="Mariateresa" last="Volpicella">Mariateresa Volpicella</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Bari, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Bari</wicri:regionArea><wicri:noRegion>Bari</wicri:noRegion></affiliation></author><author><name sortKey="Henrion Caude, Alexandra" sort="Henrion Caude, Alexandra" uniqKey="Henrion Caude A" first="Alexandra" last="Henrion-Caude">Alexandra Henrion-Caude</name><affiliation wicri:level="4"><nlm:affiliation>INSERM U1163, Université Paris Descartes, Sorbonne Paris Cité, Institut Imagine, GenAtlas Platform, 24 Boulevard du Montparnasse, 75015 Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INSERM U1163, Université Paris Descartes, Sorbonne Paris Cité, Institut Imagine, GenAtlas Platform, 24 Boulevard du Montparnasse, 75015 Paris</wicri:regionArea><wicri:noRegion>75015 Paris</wicri:noRegion><placeName><settlement type="city">Paris</settlement><region type="région" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName><orgName type="university">Université Paris-Descartes</orgName></affiliation></author><author><name sortKey="Nabavi, S M" sort="Nabavi, S M" uniqKey="Nabavi S" first="S M" last="Nabavi">S M Nabavi</name><affiliation wicri:level="1"><nlm:affiliation>Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.</nlm:affiliation><country xml:lang="fr">Iran</country><wicri:regionArea>Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran</wicri:regionArea><wicri:noRegion>Tehran</wicri:noRegion></affiliation></author><author><name sortKey="Vacca, R A" sort="Vacca, R A" uniqKey="Vacca R" first="R A" last="Vacca">R A Vacca</name><affiliation wicri:level="1"><nlm:affiliation>Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies, National Council of Research, Bari, Italy. Electronic address: r.vacca@ibiom.cnr.it.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies, National Council of Research, Bari</wicri:regionArea><wicri:noRegion>Bari</wicri:noRegion></affiliation></author></analytic><series><title level="j">Free radical biology & medicine</title><idno type="eISSN">1873-4596</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Mitochondria play a pivotal role in cellular energy-generating processes and are considered master regulators of cell life and death fate. Mitochondrial function integrates signalling networks in several metabolic pathways controlling neurogenesis and neuroplasticity. Indeed, dysfunctional mitochondria and mitochondrial-dependent activation of intracellular stress cascades are critical initiating events in many human neurodegenerative or neurodevelopmental diseases including Down syndrome (DS). It is well established that trisomy of human chromosome 21 can cause DS. DS is associated with neurodevelopmental delay, intellectual disability and early neurodegeneration. Recently, molecular mechanisms responsible for mitochondrial damage and energy deficits have been identified and characterized in several DS-derived human cells and animal models of DS. Therefore, therapeutic strategies targeting mitochondria could have great potential for new treatment regimens in DS. The purpose of this review is to highlight recent studies concerning mitochondrial impairment in DS, focusing on alterations of the molecular pathways controlling mitochondrial function. We will also discuss the effects and molecular mechanisms of naturally occurring and chemically synthetized drugs that exert neuroprotective effects through modulation of mitochondrial function and attenuation of oxidative stress. These compounds might represent novel therapeutic tools for the modulation of energy deficits in DS.</div></front></TEI><affiliations><list><country><li>Australie</li><li>Autriche</li><li>France</li><li>Iran</li><li>Italie</li></country><region><li>Toscane</li><li>Vienne (Autriche)</li><li>Île-de-France</li></region><settlement><li>Paris</li><li>Pise</li><li>Vienne (Autriche)</li></settlement><orgName><li>Université Paris-Descartes</li><li>Université de Pise</li></orgName></list><tree><country name="Italie"><noRegion><name sortKey="Valenti, Daniela" sort="Valenti, Daniela" uniqKey="Valenti D" first="Daniela" last="Valenti">Daniela Valenti</name></noRegion><name sortKey="De Rasmo, Domenico" sort="De Rasmo, Domenico" uniqKey="De Rasmo D" first="Domenico" last="De Rasmo">Domenico De Rasmo</name><name sortKey="Rossi, Leonardo" sort="Rossi, Leonardo" uniqKey="Rossi L" first="Leonardo" last="Rossi">Leonardo Rossi</name><name sortKey="Signorile, Anna" sort="Signorile, Anna" uniqKey="Signorile A" first="Anna" last="Signorile">Anna Signorile</name><name sortKey="Vacca, R A" sort="Vacca, R A" uniqKey="Vacca R" first="R A" last="Vacca">R A Vacca</name><name sortKey="Volpicella, Mariateresa" sort="Volpicella, Mariateresa" uniqKey="Volpicella M" first="Mariateresa" last="Volpicella">Mariateresa Volpicella</name></country><country name="Australie"><noRegion><name sortKey="Braidy, Nady" sort="Braidy, Nady" uniqKey="Braidy N" first="Nady" last="Braidy">Nady Braidy</name></noRegion></country><country name="Autriche"><region name="Vienne (Autriche)"><name sortKey="Atanasov, A G" sort="Atanasov, A G" uniqKey="Atanasov A" first="A G" last="Atanasov">A G Atanasov</name></region></country><country name="France"><region name="Île-de-France"><name sortKey="Henrion Caude, Alexandra" sort="Henrion Caude, Alexandra" uniqKey="Henrion Caude A" first="Alexandra" last="Henrion-Caude">Alexandra Henrion-Caude</name></region></country><country name="Iran"><noRegion><name sortKey="Nabavi, S M" sort="Nabavi, S M" uniqKey="Nabavi S" first="S M" last="Nabavi">S M Nabavi</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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