首页> 外文期刊>Journal of Neurochemistry: Offical Journal of the International Society for Neurochemistry >Lipid peroxidation is essential for alpha-synuclein-induced cell death
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Lipid peroxidation is essential for alpha-synuclein-induced cell death

机译:脂质过氧化对于α-突触核蛋白诱导的细胞死亡至关重要

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摘要

Parkinson's disease is the second most common neurodegenerative disease and its pathogenesis is closely associated with oxidative stress. Deposition of aggregated alpha-synuclein (alpha-Syn) occurs in familial and sporadic forms of Parkinson's disease. Here, we studied the effect of oligomeric alpha-Syn on one of the major markers of oxidative stress, lipid peroxidation, in primary co-cultures of neurons and astrocytes. We found that oligomeric but not monomeric alpha-Syn significantly increases the rate of production of reactive oxygen species, subsequently inducing lipid peroxidation in both neurons and astrocytes. Pre-incubation of cells with isotope-reinforced polyunsaturated fatty acids (D-PUFAs) completely prevented the effect of oligomeric alpha-Syn on lipid peroxidation. Inhibition of lipid peroxidation with D-PUFAs further protected cells from cell death induced by oligomeric alpha-Syn. Thus, lipid peroxidation induced by misfolding of alpha-Syn may play an important role in the cellular mechanism of neuronal cell loss in Parkinson's disease.
机译:帕金森氏病是第二大最常见的神经退行性疾病,其发病机理与氧化应激密切相关。聚集的α-突触核蛋白(α-Syn)的沉积以帕金森氏病的家族和散发形式发生。在这里,我们研究了在神经元和星形胶质细胞的初级共培养物中,寡聚α-Syn对氧化应激,脂质过氧化的主要标志之一的影响。我们发现寡聚而不是单体的α-Syn可以显着提高活性氧的产生速率,随后在神经元和星形胶质细胞中诱导脂质过氧化。将细胞与同位素增强的多不饱和脂肪酸(D-PUFAs)预先孵育,可以完全防止寡聚α-Syn对脂质过氧化的影响。用D-PUFA抑制脂质过氧化进一步保护细胞免受寡聚α-Syn诱导的细胞死亡。因此,由α-Syn的错误折叠引起的脂质过氧化可能在帕金森氏病的神经元细胞损失的细胞机制中起重要作用。

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