Titre :

Alpha synuclein determines ferroptosis sensitivity in dopaminergic neurons via modulation of ether-phospholipid membrane composition.

Auteur(s) :

Mahoney Sanchez, Laura [Auteur]
Lille Neurosciences & Cognition - U 1172 [LilNCog]
Bouchaoui, Hind [Auteur]
Lille Neurosciences & Cognition - U 1172 [LilNCog]
Boussaad, I. [Auteur]
Jonneaux, Aurelie [Auteur]
Lille Neurosciences & Cognition - U 1172 [LilNCog]
Timmerman, Kelly [Auteur]
Lille Neurosciences & Cognition - U 1172 [LilNCog]
Berdeaux, O. [Auteur]
Ayton, S. [Auteur]
Krüger, R. [Auteur]
Duce, James A. [Auteur]
University of Melbourne
Devos, David [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Devedjan, Jean-Christophe [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172

Titre de la revue :

Cell Reports

Nom court de la revue :

Cell Rep

Numéro :

40

Pagination :

111231

Éditeur :

Cell Press

Date de publication :

2022-08-26

ISSN :

2211-1247

Discipline(s) HAL :

Sciences du Vivant [q-bio]

Résumé en anglais : [en]

There is a continued unmet need for treatments that can slow Parkinson’s disease progression due to the lack of understanding behind the molecular mechanisms underlying neurodegeneration. Since its discovery, ferroptosis ...
Lire la suite >There is a continued unmet need for treatments that can slow Parkinson’s disease progression due to the lack of understanding behind the molecular mechanisms underlying neurodegeneration. Since its discovery, ferroptosis has been implicated in several diseases and represents a therapeutic target in Parkinson’s disease. Here, we use two highly relevant human dopaminergic neuronal models to show that endogenous levels of α-synuclein can determine the sensitivity of dopaminergic neurons to ferroptosis. We show that reducing α-synuclein expression in dopaminergic neurons leads to ferroptosis evasion, while elevated α-synuclein expression in patients’ small-molecule-derived neuronal precursor cells with SNCA triplication causes an increased vulnerability to lipid peroxidation and ferroptosis. Lipid profiling reveals that ferroptosis resistance is due to a reduction in ether-linked phospholipids, required for ferroptosis, in neurons depleted of α-synuclein (α-syn). These results provide a molecular mechanism linking α-syn levels to the sensitivity of dopaminergic neurons to ferroptosis, suggesting potential therapeutic relevance.Lire moins >

Langue :

Anglais

Audience :

Internationale

Vulgarisation :

Non

Établissement(s) :

Université de Lille
Inserm
CHU Lille

Collections :

• Lille Neurosciences & Cognition (LilNCog) - U 1172

Date de dépôt :

2024-06-24T21:17:56Z
2024-11-06T10:47:55Z