Ferroptosis, a newly characterized form of cell death in Parkinson's disease that is regulated by PKC.
By B. Do Van, F. Gouel, A. Jonneaux, Kelly Timmerman, P. Gele, M. Pétrault, M. Bastide, C. Laloux, C. Moreau, R. Bordet and 2 more. Neurobiology of Disease, 2016
615 citations recorded by the source corpus.
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.
Subfields: Molecular Biology, Oncology, Pulmonary and Respiratory Medicine
View Paper: https://www.semanticscholar.org/paper/ca011c954454754e72129f25fb0ea55fa6b58b77
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Citations in the corpus
- Ferroptosis: mechanisms and links with diseases (2021, background): “Besides, ferroptosis inhibitors are protective in cellular models of Huntington’s disease,(253) and an MPTP mouse model of Parkinson’s disease.(254) Recently promising results were reported for the use of an anti-ferroptotic compound in phase I clinical trials in amyotrophic lateral sclerosis (ALS) ”
- Neuronal Cell Death. (2018, positive): “Transcriptional markers associated with ferroptosis are increased in Parkinson’s disease substantia niagra samples, and ferrostatin-1 blocks 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neuronal loss and accompanying motor impairment in a mouse model (177).”
- Role of Mitochondria in Ferroptosis (2018, background): “A role of ferroptosis in neurodegeneration has also been implicated (Chen et al., 2015; Do Van et al., 2016; Skouta et al., 2014).”
- Inhibition of neuronal ferroptosis protects hemorrhagic brain. (2017, background): “To date, ferroptosis has been reported in one model of Parkinson’s disease, but it has not been shown in an in vivo stroke model (37).”
- Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease. (2017, positive): “…Huntington´s, and Alzheimer´s Diseases, as well as in other forms of neurodegeneration and traumatic and hemorrhagic brain injury (Chen et al., 2015; Do Van et al., 2016; Gascon et al., 2016; Guiney et al., 2017; Hambright et al., 2017; Li et al., 2017; Skouta et al., 2014; Zille et al., 2017).”
- Iron Metabolism in Ferroptosis (2020, background): “In differentiated Lund human mesencephalic cells, deferiprone is able to specifically inhibit erastin- and glutamate-induced ferroptosis (Do Van et al., 2016).”
- Molecular mechanisms of cell death in neurological diseases (2021, background): “The canonical RTA ferroptosis inhibitors liproxstatin-1 and ferrostatin-1 have been reported to exhibit efficacy in mouse models of stroke [110], PD [111] and HD slice culture assays [112].”