Ferroptosis, a newly characterized form of cell death in Parkinson's disease that is regulated by PKC.
Identifieur interne : 001A23 ( Ncbi/Checkpoint ); précédent : 001A22; suivant : 001A24Ferroptosis, a newly characterized form of cell death in Parkinson's disease that is regulated by PKC.
Auteurs : Bruce Do Van [France] ; Flore Gouel [France] ; Aurélie Jonneaux [France] ; Kelly Timmerman [France] ; Patrick Gelé [France] ; Maud Pétrault [France] ; Michèle Bastide [France] ; Charlotte Laloux [France] ; Caroline Moreau [France] ; Régis Bordet [France] ; David Devos [France] ; Jean-Christophe Devedjian [France]Source :
- Neurobiology of disease [ 1095-953X ] ; 2016.
Abstract
Parkinson's disease (PD) is a complex illness characterized by progressive dopaminergic neuronal loss. Several mechanisms associated with the iron-induced death of dopaminergic cells have been described. Ferroptosis is an iron-dependent, regulated cell death process that was recently described in cancer. Our present work show that ferroptosis is an important cell death pathway for dopaminergic neurons. Ferroptosis was characterized in Lund human mesencephalic cells and then confirmed ex vivo (in organotypic slice cultures) and in vivo (in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model). Some of the observed characteristics of ferroptosis differed from those reported previously. For example, ferroptosis may be initiated by PKCα activation, which then activates MEK in a RAS-independent manner. The present study is the first to emphasize the importance of ferroptosis dysregulation in PD. In neurodegenerative diseases like PD, iron chelators, Fer-1 derivatives and PKC inhibitors may be strong drug candidates to pharmacologically modulate the ferroptotic signaling cascade.
DOI: 10.1016/j.nbd.2016.05.011
PubMed: 27189756
Affiliations:
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France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Medical Pharmacology/INSERM U1171, Lille Faculty of Medicine, Lille Nord de France University, Lille</wicri:regionArea><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation></author><author><name sortKey="Gouel, Flore" sort="Gouel, Flore" uniqKey="Gouel F" first="Flore" last="Gouel">Flore Gouel</name><affiliation wicri:level="3"><nlm:affiliation>Department of Medical Pharmacology/INSERM U1171, Lille Faculty of Medicine, Lille Nord de France University, Lille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Medical Pharmacology/INSERM U1171, Lille Faculty of Medicine, Lille Nord de France University, Lille</wicri:regionArea><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation></author><author><name sortKey="Jonneaux, Aurelie" sort="Jonneaux, Aurelie" uniqKey="Jonneaux A" first="Aurélie" last="Jonneaux">Aurélie Jonneaux</name><affiliation wicri:level="3"><nlm:affiliation>Department of Medical Pharmacology/INSERM U1171, Lille Faculty of Medicine, Lille Nord de France University, Lille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Medical Pharmacology/INSERM U1171, Lille Faculty of Medicine, Lille Nord de France University, Lille</wicri:regionArea><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation></author><author><name sortKey="Timmerman, Kelly" sort="Timmerman, Kelly" uniqKey="Timmerman K" first="Kelly" last="Timmerman">Kelly Timmerman</name><affiliation wicri:level="3"><nlm:affiliation>Department of Medical Pharmacology/INSERM U1171, Lille Faculty of Medicine, Lille Nord de France University, Lille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Medical Pharmacology/INSERM U1171, Lille Faculty of Medicine, Lille Nord de France University, Lille</wicri:regionArea><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation></author><author><name sortKey="Gele, Patrick" sort="Gele, Patrick" uniqKey="Gele P" first="Patrick" last="Gelé">Patrick Gelé</name><affiliation wicri:level="3"><nlm:affiliation>Biological Resources Centre, Lille University Hospital, Lille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Biological Resources Centre, Lille University Hospital, Lille</wicri:regionArea><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation></author><author><name sortKey="Petrault, Maud" sort="Petrault, Maud" uniqKey="Petrault M" first="Maud" last="Pétrault">Maud Pétrault</name><affiliation wicri:level="3"><nlm:affiliation>Department of Medical Pharmacology/INSERM U1171, Lille Faculty of Medicine, Lille Nord de France University, Lille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Medical Pharmacology/INSERM U1171, Lille Faculty of Medicine, Lille Nord de France University, Lille</wicri:regionArea><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation></author><author><name sortKey="Bastide, Michele" sort="Bastide, Michele" uniqKey="Bastide M" first="Michèle" last="Bastide">Michèle Bastide</name><affiliation wicri:level="3"><nlm:affiliation>Department of Medical Pharmacology/INSERM U1171, Lille Faculty of Medicine, Lille Nord de France University, Lille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Medical Pharmacology/INSERM U1171, Lille Faculty of Medicine, Lille Nord de France University, Lille</wicri:regionArea><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation></author><author><name sortKey="Laloux, Charlotte" sort="Laloux, Charlotte" uniqKey="Laloux C" first="Charlotte" last="Laloux">Charlotte Laloux</name><affiliation wicri:level="3"><nlm:affiliation>Department of Medical Pharmacology/INSERM U1171, Lille Faculty of Medicine, Lille Nord de France University, Lille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Medical Pharmacology/INSERM U1171, Lille Faculty of Medicine, Lille Nord de France University, Lille</wicri:regionArea><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation></author><author><name sortKey="Moreau, Caroline" sort="Moreau, Caroline" uniqKey="Moreau C" first="Caroline" last="Moreau">Caroline Moreau</name><affiliation wicri:level="3"><nlm:affiliation>Department of Movement Disorders and Neurology, Lille Nord de France University, Lille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Movement Disorders and Neurology, Lille Nord de France University, Lille</wicri:regionArea><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation></author><author><name sortKey="Bordet, Regis" sort="Bordet, Regis" uniqKey="Bordet R" first="Régis" last="Bordet">Régis Bordet</name><affiliation wicri:level="3"><nlm:affiliation>Department of Medical Pharmacology/INSERM U1171, Lille Faculty of Medicine, Lille Nord de France University, Lille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Medical Pharmacology/INSERM U1171, Lille Faculty of Medicine, Lille Nord de France University, Lille</wicri:regionArea><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation></author><author><name sortKey="Devos, David" sort="Devos, David" uniqKey="Devos D" first="David" last="Devos">David Devos</name><affiliation wicri:level="3"><nlm:affiliation>Department of Medical Pharmacology/INSERM U1171, Lille Faculty of Medicine, Lille Nord de France University, Lille, France; Biological Resources Centre, Lille University Hospital, Lille, France; Department of Movement Disorders and Neurology, Lille Nord de France University, Lille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Medical Pharmacology/INSERM U1171, Lille Faculty of Medicine, Lille Nord de France University, Lille, France; Biological Resources Centre, Lille University Hospital, Lille, France; Department of Movement Disorders and Neurology, Lille Nord de France University, Lille</wicri:regionArea><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation></author><author><name sortKey="Devedjian, Jean Christophe" sort="Devedjian, Jean Christophe" uniqKey="Devedjian J" first="Jean-Christophe" last="Devedjian">Jean-Christophe Devedjian</name><affiliation wicri:level="3"><nlm:affiliation>Department of Medical Pharmacology/INSERM U1171, Lille Faculty of Medicine, Lille Nord de France University, Lille, France; Biological Resources Centre, Lille University Hospital, Lille, France; Department of Movement Disorders and Neurology, Lille Nord de France University, Lille, France; University of the Littoral Opal Coast, Calais, France. Electronic address: Jean-Christophe.Devedjian@univ-littoral.fr.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Medical Pharmacology/INSERM U1171, Lille Faculty of Medicine, Lille Nord de France University, Lille, France; Biological Resources Centre, Lille University Hospital, Lille, France; Department of Movement Disorders and Neurology, Lille Nord de France University, Lille, France; University of the Littoral Opal Coast, Calais</wicri:regionArea><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Calais</settlement></placeName></affiliation></author></analytic><series><title level="j">Neurobiology of disease</title><idno type="eISSN">1095-953X</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">Parkinson's disease (PD) is a complex illness characterized by progressive dopaminergic neuronal loss. Several mechanisms associated with the iron-induced death of dopaminergic cells have been described. Ferroptosis is an iron-dependent, regulated cell death process that was recently described in cancer. Our present work show that ferroptosis is an important cell death pathway for dopaminergic neurons. Ferroptosis was characterized in Lund human mesencephalic cells and then confirmed ex vivo (in organotypic slice cultures) and in vivo (in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model). Some of the observed characteristics of ferroptosis differed from those reported previously. For example, ferroptosis may be initiated by PKCα activation, which then activates MEK in a RAS-independent manner. The present study is the first to emphasize the importance of ferroptosis dysregulation in PD. In neurodegenerative diseases like PD, iron chelators, Fer-1 derivatives and PKC inhibitors may be strong drug candidates to pharmacologically modulate the ferroptotic signaling cascade.</div></front></TEI><affiliations><list><country><li>France</li></country><region><li>Hauts-de-France</li><li>Nord-Pas-de-Calais</li></region><settlement><li>Calais</li><li>Lille</li></settlement></list><tree><country name="France"><region name="Hauts-de-France"><name sortKey="Do Van, Bruce" sort="Do Van, Bruce" uniqKey="Do Van B" first="Bruce" last="Do Van">Bruce Do Van</name></region><name sortKey="Bastide, Michele" sort="Bastide, Michele" uniqKey="Bastide M" first="Michèle" last="Bastide">Michèle Bastide</name><name sortKey="Bordet, Regis" sort="Bordet, Regis" uniqKey="Bordet R" first="Régis" last="Bordet">Régis Bordet</name><name sortKey="Devedjian, Jean Christophe" sort="Devedjian, Jean Christophe" uniqKey="Devedjian J" first="Jean-Christophe" last="Devedjian">Jean-Christophe Devedjian</name><name sortKey="Devos, David" sort="Devos, David" uniqKey="Devos D" first="David" last="Devos">David Devos</name><name sortKey="Gele, Patrick" sort="Gele, Patrick" uniqKey="Gele P" first="Patrick" last="Gelé">Patrick Gelé</name><name sortKey="Gouel, Flore" sort="Gouel, Flore" uniqKey="Gouel F" first="Flore" last="Gouel">Flore Gouel</name><name sortKey="Jonneaux, Aurelie" sort="Jonneaux, Aurelie" uniqKey="Jonneaux A" first="Aurélie" last="Jonneaux">Aurélie Jonneaux</name><name sortKey="Laloux, Charlotte" sort="Laloux, Charlotte" uniqKey="Laloux C" first="Charlotte" last="Laloux">Charlotte Laloux</name><name sortKey="Moreau, Caroline" sort="Moreau, Caroline" uniqKey="Moreau C" first="Caroline" last="Moreau">Caroline Moreau</name><name sortKey="Petrault, Maud" sort="Petrault, Maud" uniqKey="Petrault M" first="Maud" last="Pétrault">Maud Pétrault</name><name sortKey="Timmerman, Kelly" sort="Timmerman, Kelly" uniqKey="Timmerman K" first="Kelly" last="Timmerman">Kelly Timmerman</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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