期刊
NEUROBIOLOGY OF DISEASE
卷 94, 期 -, 页码 169-178出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2016.05.011
关键词
Parkinson's disease; Ferroptosis; Lund human mesencephalic cells; 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model
资金
- French Ministry of Health [2008-006842-25]
- PHRC grants
- DN2M regional grant [DN2M2015]
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 PKC alpha 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. (C) 2016 Elsevier Inc. All rights reserved.
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