DJ-1 protein has multiple specific mechanisms to protect dopaminergic neurons against neurodegeneration in Parkinson's disease. Wild type DJ-1 can acts as oxidative stress sensor and as an antioxidant. DJ-1 exhibits the properties of molecular chaperone, protease, glyoxalase, transcriptional regulator that protects mitochondria from oxidative stress. DJ-1 increases the expression of two mitochondrial uncoupling proteins (UCP 4 and UCP5), that decrease mitochondrial membrane potential and leads to the suppression of ROS production, optimizes of a number of mitochondrial functions, and is regarded as protection for the neuronal cell survival. We discuss also the stabilizing interaction of DJ-1 with the mitochondrial Bcl-xL protein, which regulates the activity of (Inositol trisphosphate receptor) IP3R, prevents the cytochrome c release from mitochondria and inhibits the apoptosis activation. Upon oxidative stress DJ-1 is able to regulate various transcription factors including nuclear factor Nrf2, PI3K/PKB, and p53 signal pathways. Stress-activated transcription factor Nrf2 regulates the pathways to protect cells against oxidative stress and metabolic pathways initiating the NADPH and ATP production. DJ-1 induces the Nrf2 dissociation from its inhibitor Keap1 (Kelch-like ECH-associated protein 1), promoting Nrf2 nuclear translocation and binding to antioxidant response elements. DJ-1 is shown to be a co-activator of the transcription factor NF-kB. Under nitrosative stress, DJ-1 may regulate PI3K/PKB signaling through PTEN transnitrosylation, which leads to inhibition of phosphatase activity. DJ-1 has a complex modulating effect on the p53 pathway: one side DJ-1 directly binds to p53 to restore its transcriptional activity and on the other hand DJ-1 can stimulate deacylation and suppress p53 transcriptional activity. The ability of the DJ-1 to induce activation of different transcriptional factors and change redox balance protect neurons against aggregation of α-synuclein and oligomer-induced neurodegeneration.

中文翻译：

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DJ-1在帕金森氏病发病机理中的作用。

DJ-1蛋白具有多种保护多巴胺能神经元免受帕金森氏病神经退行性变的特定机制。野生型DJ-1可用作氧化应激传感器和抗氧化剂。DJ-1具有分子伴侣，蛋白酶，乙二醛酶，保护线粒体免受氧化应激的转录调节剂的特性。DJ-1可增加两种线粒体解偶联蛋白（UCP 4和UCP5）的表达，从而降低线粒体膜电位并导致ROS的产生受到抑制，优化了许多线粒体功能，并被视为对神经元细胞存活的保护。我们还将讨论DJ-1与线粒体Bcl-xL蛋白的稳定相互作用，该蛋白调节（肌醇三磷酸受体）IP3R的活性，阻止细胞色素c从线粒体释放，并抑制凋亡激活。在氧化应激下，DJ-1能够调节各种转录因子，包括核因子Nrf2，PI3K / PKB和p53信号通路。应激激活的转录因子Nrf2调节该途径，以保护细胞免受氧化应激和代谢途径的破坏，从而启动NADPH和ATP的产生。DJ-1诱导Nrf2从其抑制剂Keap1（Kelch样ECH相关蛋白1）解离，促进Nrf2核易位并结合抗氧化反应元件。已显示DJ-1是转录因子NF-kB的共激活因子。在亚硝化胁迫下，DJ-1可能通过PTEN反硝化作用调节PI3K / PKB信号传导，从而抑制磷酸酶活性。DJ-1对p53途径具有复杂的调节作用：DJ-1的一侧直接与p53结合以恢复其转录活性，另一方面DJ-1可以刺激脱酰基并抑制p53转录活性。DJ-1诱导不同转录因子激活和改变氧化还原平衡的能力可保护神经元免受α-突触核蛋白的聚集和寡聚体诱导的神经变性。