Ferroptosis, a newly characterized form of cell death in Parkinson's disease that is regulated by PKC.
Identifieur interne : 000280 ( Main/Exploration ); précédent : 000279; suivant : 000281Ferroptosis, 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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<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>
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<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>
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