Alpha lipoic acid ameliorates motor deficits by inhibiting ferroptosis in Parkinson's disease.
Neurosci Lett
; 810: 137346, 2023 07 27.
Article
em En
| MEDLINE
| ID: mdl-37308056
ABSTRACT
Parkinson's disease (PD) is a neurodegenerative disease. Ferroptosis shares several features with PD pathophysiology, and anti-ferroptosis molecules are neuroprotective in PD animal models. As an antioxidant and iron chelating agent, alpha lipoic acid (ALA) has a neuroprotective effect on PD; however, the influence of ALA on ferroptosis in PD remains unclear. This study aimed to determine the mechanism of ALA in regulating ferroptosis in PD models. Results showed that ALA could ameliorate motor deficits in PD models and regulate iron metabolism by upregulating ferroportin (FPN) and ferritin heavy chain 1 (FTH1) and downregulating iron importer divalent metal transporter 1 (DMT1). Moreover, ALA decreased the accumulation of reactive oxygen species (ROS) and lipid peroxidation, rescued mitochondrial damage, and prevented ferroptosis effectively by inhibiting the downregulation of glutathione peroxidase 4 (GPX4) and cysteine/glutamate transporter (xCT) in PD. Mechanistic study indicated that the activation of SIRT1/NRF2 pathway was involved in the upregulation effect of GPX4 and FTH1. Thus, ALA ameliorates motor deficits in PD models by regulating iron metabolism and mitigating ferroptosis through the SIRT1/NRF2 signaling pathway.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doença de Parkinson
/
Ácido Tióctico
/
Doenças Neurodegenerativas
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Neurosci Lett
Ano de publicação:
2023
Tipo de documento:
Article