Titre :

ACSL4 and the lipoxygenases 15/15B are pivotal for ferroptosis induced by iron and PUFA dyshomeostasis in dopaminergic neurons

Auteur(s) :

Bouchaoui, Hind [Auteur]
Impact de l'environnement chimique sur la santé humaine - ULR 4483 [IMPECS]
Lille Neurosciences & Cognition - U 1172 [LilNCog]
Mahoney Sanchez, Laura [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Garçon, Guillaume [Auteur]
IMPact de l'Environnement Chimique sur la Santé humaine (IMPECS) - ULR 4483
Berdeaux, Olivier [Auteur]
Alleman, Laurent [Auteur]
Centre for Energy and Environment [CERI EE - IMT Nord Europe]
Devos, David [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Duce, James A. [Auteur]
Devedjian, Jean-Christophe [Auteur]
Université du Littoral Côte d'Opale [ULCO]
Lille Neurosciences & Cognition - U 1172 [LilNCog]

Titre de la revue :

Free Radical Biology and Medicine

Nom court de la revue :

Free Radic Biol Med

Numéro :

195

Pagination :

145-157

Éditeur :

Elsevier

Date de publication :

2022-12-26

ISSN :

0891-5849

Mot(s)-clé(s) en anglais :

Parkinson's disease
Ferroptosis
Arachidonic acid
Iron
Lipid peroxidation
Dopaminergic neurons

Discipline(s) HAL :

Sciences du Vivant [q-bio]
Sciences du Vivant [q-bio]/Médecine humaine et pathologie
Sciences du Vivant [q-bio]/Neurosciences [q-bio.NC]

Résumé en anglais : [en]

Ferroptosis, an iron-dependent regulated cell death triggered by high lipid peroxide levels, has been implicated in several neurodegenerative diseases, including Parkinson's disease (PD). Brain regions such as the striatum ...
Lire la suite >Ferroptosis, an iron-dependent regulated cell death triggered by high lipid peroxide levels, has been implicated in several neurodegenerative diseases, including Parkinson's disease (PD). Brain regions such as the striatum are highly rich in both peroxidation susceptible PUFAs and iron, which accumulate at a greater rate than age in PD. The exact molecular pathways and patho-physiological conditions promoting cell death in the dopaminergic neurons that are particularly susceptible in PD remain elusive. In the current work, we show that modifying the PUFA composition in membranes of dopaminergic neurons using arachidonic acid (AA) can determine ferroptosis susceptibility. Furthermore, cotreatment with iron (Fe), increases AA-containing phospholipid association and synergistically promotes high lipid peroxidation to facilitate ferroptosis. Ex vivo analysis with organotypic brain slices, confirm that AA + Fe induces cell death in the nigrostriatal pathway and can be rescued by the anti-ferroptotic drug Ferrostatin-1. Prevention of ferroptotic AA + Fe induced cell death through inhibition of ACSL4, ALOX15 or ALOX15B provides mechanistic support of this lipid peroxidation pathway being involved in dopaminergic neuronal death and novel potential pharmacological targets for neuroprotective strategies in PD.Lire moins >

Langue :

Anglais

Comité de lecture :

Oui

Audience :

Internationale

Vulgarisation :

Non

Établissement(s) :

Université de Lille
CHU Lille
Institut Pasteur de Lille

Collections :

• IMPact de l'Environnement Chimique sur la Santé humaine (IMPECS) - ULR 4483
• Lille Neurosciences & Cognition (LilNCog) - U 1172

Équipe(s) de recherche :

Troubles cognitifs dégénératifs et vasculaires

Date de dépôt :

2023-10-20T05:55:05Z
2024-02-29T14:51:51Z