Neuroprotective and anti-inflammatory effects of linoleic acid in models of parkinson’s disease: the implication of lipid droplets and lipophagy

Parkinson’s disease (PD) is the second most prevalent neurodegenerative disease after Alzheimer’s disease. The principal pathological feature of PD is the progressive loss of dopaminergic neurons in the ventral midbrain. This pathology involves several cellular alterations: oxidative stress, mitocho...

Descripción completa

Detalles Bibliográficos
Autores: Alarcón-Gil, Jesús, Sierra-Magro, Ana, Morales-García, José A., Sanz-SanCristóbal, Marina, Alonso-Gil, Sandra, Cortés-Canteli, Marta, Niso-Santano, Mireia, Martinez-Chacon, Guadalupe, Fuentes, José M., Santos, Ángel, Pérez-Castillo, Ana
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/289766
Acceso en línea:http://hdl.handle.net/10261/289766
Access Level:acceso abierto
Palabra clave:Autophagy
Lipophagy
Neurodegeneration
Lipid droplets
Oxidative Stress
Descripción
Sumario:Parkinson’s disease (PD) is the second most prevalent neurodegenerative disease after Alzheimer’s disease. The principal pathological feature of PD is the progressive loss of dopaminergic neurons in the ventral midbrain. This pathology involves several cellular alterations: oxidative stress, mitochondrial dysfunction, loss of proteostasis, and autophagy impairment. Moreover, in recent years, lipid metabolism alterations have become relevant in PD pathogeny. The modification of lipid metabolism has become a possible way to treat the disease. Because of this, we analyzed the effect and possible mechanism of action of linoleic acid (LA) on an SH-SY5Y PD cell line model and a PD mouse model, both induced by 6-hydroxydopamine (6-OHDA) treatment. The results show that LA acts as a potent neuroprotective and anti-inflammatory agent in these PD models. We also observed that LA stimulates the biogenesis of lipid droplets and improves the autophagy/lipophagy flux, which resulted in an antioxidant effect in the in vitro PD model. In summary, we confirmed the neuroprotective effect of LA in vitro and in vivo against PD. We also obtained some clues about the novel neuroprotective mechanism of LA against PD through the regulation of lipid droplet dynamics.