Lipid peroxidation is essential for α-synuclein-induced cell death.
Lipid peroxidation is essential for α-synuclein-induced cell death.
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DOI：
10.1111/jnc.13024
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发表时间：
2015-05
影响因子：
4.7
通讯作者：
Shchepinov MS
中科院分区：
文献类型：
--
作者：
Angelova PR;Horrocks MH;Klenerman D;Gandhi S;Abramov AY;Shchepinov MS
帕金森病是第二常见的神经退行性疾病，其发病机制与氧化应激密切相关。聚集的α-突触核蛋白（α-Syn）沉积发生在家族性和散发性帕金森病中。在这里，我们研究了寡聚体α-Syn对神经元和星形胶质细胞原代共培养物中氧化应激的主要标志物之一脂质过氧化的影响。我们发现寡聚体而非单体α-Syn显著增加活性氧的产生速率，随后诱导神经元和星形胶质细胞中的脂质过氧化。用同位素增强的多不饱和脂肪酸（D-PUFA）预孵育细胞完全阻止了寡聚体α-Syn对脂质过氧化的影响。用D-PUFAs抑制脂质过氧化进一步保护细胞免受寡聚体α-Syn诱导的细胞死亡。因此，由α-Syn错误折叠诱导的脂质过氧化可能在帕金森病神经元细胞丢失的细胞机制中发挥重要作用。 我们发现聚集的α-突触核蛋白诱导活性氧（ROS）的产生，随后刺激神经元和星形胶质细胞的脂质过氧化和细胞死亡。通过与增强的多不饱和脂肪酸（D-PUFA）孵育特异性抑制脂质过氧化，完全阻止了α-突触核蛋白对脂质过氧化和细胞死亡的影响。
Parkinson's disease is the second most common neurodegenerative disease and its pathogenesis is closely associated with oxidative stress. Deposition of aggregated α‐synuclein (α‐Syn) occurs in familial and sporadic forms of Parkinson's disease. Here, we studied the effect of oligomeric α‐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 α‐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 α‐Syn on lipid peroxidation. Inhibition of lipid peroxidation with D‐PUFAs further protected cells from cell death induced by oligomeric α‐Syn. Thus, lipid peroxidation induced by misfolding of α‐Syn may play an important role in the cellular mechanism of neuronal cell loss in Parkinson's disease. We have found that aggregated α‐synuclein‐induced production of reactive oxygen species (ROS) that subsequently stimulates lipid peroxidation and cell death in neurons and astrocytes. Specific inhibition of lipid peroxidation by incubation with reinforced polyunsaturated fatty acids (D‐PUFAs) completely prevented the effect of α‐synuclein on lipid peroxidation and cell death.
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影响因子：
3.7
作者：
Fecchio, Chiara;De Franceschi, Giorgia;de Laureto, Patrizia Polverino
通讯作者：
de Laureto, Patrizia Polverino
DOI：
10.1084/jem.182.2.367
发表时间：
1995-08-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Zamzami N;Marchetti P;Castedo M;Decaudin D;Macho A;Hirsch T;Susin SA;Petit PX;Mignotte B;Kroemer G
通讯作者：
Kroemer G
影响因子：
16.2
作者：
Sharon, R;Bar-Joseph, I;Selkoe, DJ
通讯作者：
Selkoe, DJ
影响因子：
4
作者：
Suwanjang W;Holmström KM;Chetsawang B;Abramov AY
通讯作者：
Abramov AY
影响因子：
14.8
作者：
Kagan, VE;Tyurin, VA;Borisenko, GG
通讯作者：
Borisenko, GG