Format

Send to

Choose Destination
Neurobiol Dis. 2016 Oct;94:169-78. doi: 10.1016/j.nbd.2016.05.011. Epub 2016 May 14.

Ferroptosis, a newly characterized form of cell death in Parkinson's disease that is regulated by PKC.

Author information

1
Department of Medical Pharmacology/INSERM U1171, Lille Faculty of Medicine, Lille Nord de France University, Lille, France.
2
Biological Resources Centre, Lille University Hospital, Lille, France.
3
Department of Movement Disorders and Neurology, Lille Nord de France University, Lille, France.
4
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.
5
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.

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.

KEYWORDS:

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model; Ferroptosis; Lund human mesencephalic cells; Parkinson's disease

PMID:
27189756
DOI:
10.1016/j.nbd.2016.05.011
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center