title: Ferroptosis, a newly characterized form of cell death in Parkinson's disease that is regulated by PKC.
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.
authors.affiliation: Department of Medical Pharmacology/INSERM U1171, Lille Faculty of Medicine, Lille Nord de France University, Lille, France.
authors.forename: Bruce
authors.initials: B
authors.lastname: Do Van
authors.affiliation: Department of Medical Pharmacology/INSERM U1171, Lille Faculty of Medicine, Lille Nord de France University, Lille, France.
authors.forename: Flore
authors.initials: F
authors.lastname: Gouel
authors.affiliation: Department of Medical Pharmacology/INSERM U1171, Lille Faculty of Medicine, Lille Nord de France University, Lille, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Jonneaux
authors.affiliation: Department of Medical Pharmacology/INSERM U1171, Lille Faculty of Medicine, Lille Nord de France University, Lille, France.
authors.forename: Kelly
authors.initials: K
authors.lastname: Timmerman
authors.affiliation: Biological Resources Centre, Lille University Hospital, Lille, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Gelé
authors.affiliation: Department of Medical Pharmacology/INSERM U1171, Lille Faculty of Medicine, Lille Nord de France University, Lille, France.
authors.forename: Maud
authors.initials: M
authors.lastname: Pétrault
authors.affiliation: Department of Medical Pharmacology/INSERM U1171, Lille Faculty of Medicine, Lille Nord de France University, Lille, France.
authors.forename: Michèle
authors.initials: M
authors.lastname: Bastide
authors.affiliation: Department of Medical Pharmacology/INSERM U1171, Lille Faculty of Medicine, Lille Nord de France University, Lille, France.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Laloux
authors.affiliation: Department of Movement Disorders and Neurology, Lille Nord de France University, Lille, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Moreau
authors.affiliation: Department of Medical Pharmacology/INSERM U1171, Lille Faculty of Medicine, Lille Nord de France University, Lille, France.
authors.forename: Régis
authors.initials: R
authors.lastname: Bordet
authors.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.
authors.forename: David
authors.initials: D
authors.lastname: Devos
authors.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.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Devedjian
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D016923:Cell Death; D004298:Dopamine / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000378:metabolism*; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008636:Mesencephalon / Q000378:metabolism; D010300:Parkinson Disease / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology; D013378:Substantia Nigra / Q000378:metabolism*
chemical_list: D007501:Iron; D011493:Protein Kinase C; D004298:Dopamine
keywords: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model; Ferroptosis; Lund human mesencephalic cells; Parkinson's disease