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Article dans une revue

Ferroptosis and its potential role in the physiopathology of Parkinson's Disease.

Abstract : Parkinson's Disease (PD) is a common and progressive neurodegenerative disorder characterised by motor impairments as well as non-motor symptoms. While dopamine-based therapies are effective in fighting the symptoms in the early stages of the disease, a lack of neuroprotective drugs means that the disease continues to progress. Along with the traditionally recognised pathological hallmarks of dopaminergic neuronal death and intracellular α-synuclein (α-syn) depositions, iron accumulation, elevated oxidative stress and lipid peroxidation damage are further conspicuous features of PD pathophysiology. However, the underlying mechanisms linking these pathological hallmarks with neurodegeneration still remain unclear. Ferroptosis, a regulated iron dependent cell death pathway involving a lethal accumulation of lipid peroxides, shares several features with PD pathophysiology. Interestingly, α-syn has been functionally linked with the metabolism of both iron and lipid, suggesting a possible interplay between dysregulated α-syn and other PD pathological hallmarks related to ferroptosis. This review will address the importance for understanding these disease mechanisms that could be targeted therapeutically. Anti-ferroptosis molecules are neuroprotective in PD animal models and the anti-ferroptotic iron chelator, deferiprone, slowed disease progression and improved motor function in two independent clinical trials for PD. An ongoing larger multi-centre phase 2 clinical trial will confirm the therapeutic potential of deferiprone and the relevance of ferroptosis in PD. This review addresses the known pathological features of PD in relation to the ferroptosis pathway with therapeutic implications of targeting this cell death pathway.
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Soumis le : mercredi 16 juin 2021 - 08:45:13
Dernière modification le : lundi 21 juin 2021 - 16:05:32
Archivage à long terme le : : vendredi 17 septembre 2021 - 18:11:27


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Laura Mahoney-Sánchez, Hind Bouchaoui, Scott Ayton, David Devos, James A Duce, et al.. Ferroptosis and its potential role in the physiopathology of Parkinson's Disease.. Progress in Neurobiology, Elsevier, 2021, 196, pp.101890. ⟨10.1016/j.pneurobio.2020.101890⟩. ⟨hal-03261742⟩



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