Université de Bourgogne Franche-Comté, Dijon, F-21000, France; Team 'Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism' EA 7270, Inserm, F-21000, Dijon, France.
Université de Bourgogne Franche-Comté, Dijon, F-21000, France; - Inserm Research Center LNC UMR U1231 - Team "Cancer and Adaptive Immune Response", Bioactive Molecules and Health Research Group, Dijon, F-21000, France.
Free Radic Biol Med. 2019 Jun;137:46-58. doi: 10.1016/j.freeradbiomed.2019.04.016. Epub 2019 Apr 17.
In recent years, a particular interest has focused on the accumulation of fatty acids with very long chains (VLCFA) in the occurrence of neurodegenerative diseases such as Alzheimer's disease, multiple sclerosis or dementia. Indeed, it seems increasingly clear that this accumulation of VLCFA in the central nervous system is accompanied by a progressive demyelination resulting in death of neuronal cells. Nevertheless, molecular mechanisms by which VLCFA result in toxicity remain unclear. This study highlights for the first time in 3 different cellular models (oligodendrocytes 158 N, primary mouse brain culture, and patient fibroblasts) the types of cell death involved where VLCFA-induced ROS production leads to autophagy. The autophagic process protects the cell from this VLCFA-induced toxicity. Thus, autophagy in addition to oxidative stress can offer new therapeutic approaches.
近年来，人们对长链脂肪酸（VLCFA）在神经退行性疾病（如阿尔茨海默病、多发性硬化症或痴呆症）发生中的积累特别感兴趣。事实上，似乎越来越清楚的是，VLCFA 在中枢神经系统中的积累伴随着进行性脱髓鞘，导致神经元细胞死亡。然而，VLCFA 导致毒性的分子机制仍不清楚。本研究首次在 3 种不同的细胞模型（少突胶质细胞 158N、原代小鼠脑培养物和患者成纤维细胞）中强调了细胞死亡的类型，其中 VLCFA 诱导的 ROS 产生导致自噬。自噬过程可保护细胞免受这种 VLCFA 诱导的毒性。因此，除了氧化应激之外，自噬可以提供新的治疗方法。
