Targeting α-synuclein: Therapeutic options.
Identifieur interne : 001968 ( Ncbi/Curation ); précédent : 001967; suivant : 001969Targeting α-synuclein: Therapeutic options.
Auteurs : Benjamin Dehay [France] ; Mickael Decressac [Italie] ; Mathieu Bourdenx [France] ; Irene Guadagnino [Italie] ; Pierre-Olivier Fernagut [France] ; Anna Tamburrino [Italie] ; Fares Bassil [France] ; Wassilios G. Meissner [France] ; Erwan Bezard [France]Source :
- Movement disorders : official journal of the Movement Disorder Society [ 1531-8257 ] ; 2016.
Abstract
The discovery of the central role of α-synuclein (αSyn) in the pathogenesis of Parkinson's disease (PD) has powered, in the last decade, the emergence of novel relevant models of this condition based on viral vector-mediated expression of the disease-causing protein or inoculation of toxic species of αSyn. Although the development of these powerful tools and models has provided considerable insights into the mechanisms underlying neurodegeneration in PD, it has also been translated into the expansion of the landscape of preclinical therapeutic strategies. Much attention is now brought to the proteotoxic mechanisms induced by αSyn and how to block them using strategies inspired by intrinsic cellular pathways such as the enhancement of cellular clearance by the lysosomal-autophagic system, through proteasome-mediated degradation or through immunization. The important effort undertaken by several laboratories and consortia to tackle these issues and identify novel targets warrants great promise for the discovery not only of neuroprotective approaches but also of restorative strategies for PD and other synucleinopathies. In this viewpoint, we summarize the latest advances in this new area of PD research and will discuss promising approaches and ongoing challenges. © 2016 International Parkinson and Movement Disorder Society.
DOI: 10.1002/mds.26568
PubMed: 26926119
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Bordeaux</orgName></affiliation></author><author><name sortKey="Guadagnino, Irene" sort="Guadagnino, Irene" uniqKey="Guadagnino I" first="Irene" last="Guadagnino">Irene Guadagnino</name><affiliation wicri:level="1"><nlm:affiliation>Telethon Institute of Genetics and Medicine, Pozzuoli, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Telethon Institute of Genetics and Medicine, Pozzuoli</wicri:regionArea><wicri:noRegion>Pozzuoli</wicri:noRegion></affiliation></author><author><name sortKey="Fernagut, Pierre Olivier" sort="Fernagut, Pierre Olivier" uniqKey="Fernagut P" first="Pierre-Olivier" last="Fernagut">Pierre-Olivier Fernagut</name><affiliation wicri:level="4"><nlm:affiliation>Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, 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France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux</wicri:regionArea><placeName><region type="region">Nouvelle-Aquitaine</region><region type="old region">Aquitaine</region><settlement type="city">Bordeaux</settlement></placeName><orgName type="university">Université de Bordeaux</orgName></affiliation></author><author><name sortKey="Meissner, Wassilios G" sort="Meissner, Wassilios G" uniqKey="Meissner W" first="Wassilios G" last="Meissner">Wassilios G. Meissner</name><affiliation wicri:level="4"><nlm:affiliation>Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux</wicri:regionArea><placeName><region type="region">Nouvelle-Aquitaine</region><region type="old region">Aquitaine</region><settlement type="city">Bordeaux</settlement></placeName><orgName type="university">Université de Bordeaux</orgName></affiliation></author><author><name sortKey="Bezard, Erwan" sort="Bezard, Erwan" uniqKey="Bezard E" first="Erwan" last="Bezard">Erwan Bezard</name><affiliation wicri:level="4"><nlm:affiliation>Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux</wicri:regionArea><placeName><region type="region">Nouvelle-Aquitaine</region><region type="old region">Aquitaine</region><settlement type="city">Bordeaux</settlement></placeName><orgName type="university">Université de Bordeaux</orgName></affiliation></author></analytic><series><title level="j">Movement disorders : official journal of the Movement Disorder Society</title><idno type="eISSN">1531-8257</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The discovery of the central role of α-synuclein (αSyn) in the pathogenesis of Parkinson's disease (PD) has powered, in the last decade, the emergence of novel relevant models of this condition based on viral vector-mediated expression of the disease-causing protein or inoculation of toxic species of αSyn. Although the development of these powerful tools and models has provided considerable insights into the mechanisms underlying neurodegeneration in PD, it has also been translated into the expansion of the landscape of preclinical therapeutic strategies. Much attention is now brought to the proteotoxic mechanisms induced by αSyn and how to block them using strategies inspired by intrinsic cellular pathways such as the enhancement of cellular clearance by the lysosomal-autophagic system, through proteasome-mediated degradation or through immunization. The important effort undertaken by several laboratories and consortia to tackle these issues and identify novel targets warrants great promise for the discovery not only of neuroprotective approaches but also of restorative strategies for PD and other synucleinopathies. In this viewpoint, we summarize the latest advances in this new area of PD research and will discuss promising approaches and ongoing challenges. © 2016 International Parkinson and Movement Disorder Society.</div></front></TEI></record>Pour manipuler ce document sous Unix (Dilib)
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