Neuroprotection against Aminochrome Neurotoxicity: Glutathione Transferase M2-2 and DT-Diaphorase.
Neuroprotection against Aminochrome Neurotoxicity: Glutathione Transferase M2-2 and DT-Diaphorase.
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DOI：
10.3390/antiox11020296
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发表时间：
2022-01-31
期刊：
影响因子：
--
通讯作者：
Mannervik B
中科院分区：
文献类型：
--
作者：
Segura-Aguilar J;Muñoz P;Inzunza J;Varshney M;Nalvarte I;Mannervik B
谷氨酸是一种重要的抗氧化剂，在细胞抗氧化应激和亲电诱变剂和致癌物的解毒中起着至关重要的作用。谷胱甘肽转移酶是催化谷胱甘肽依赖性反应的酶，该反应导致毒性化合物的失活和结合，该过程随后是解毒产物的排泄。黑质纹状体神经元中含有神经黑素的多巴胺能神经元的变性和损失通常涉及氧化应激、神经炎症、α-突触核蛋白聚集成神经毒性寡聚体、线粒体功能障碍、蛋白质降解功能障碍和内质网应激。然而，目前还不清楚是什么触发了这些神经退行性过程。据报道，氨基色素可以引起所有这些机制，有趣的是，氨基色素是在神经黑色素合成过程中在含有神经黑色素的多巴胺能神经元内形成的。氨基色素是神经黑色素合成中形成的神经毒性邻醌。然而，神经毒素氨基色素是在神经黑色素合成过程中产生的，这似乎是矛盾的，尽管健康的老年人在他们死后这些神经元完好无损。这种矛盾的解释是存在的保护工具，对氨基色素神经毒性的酶DT-心肌黄酶，在这些神经元中表达，和谷胱甘肽转移酶M2-2，在星形胶质细胞中表达。最近，据报道，多巴胺能神经元可以保护谷胱甘肽转移酶M2-2从星形胶质细胞，分泌外泌体含有保护酶。
Glutathione is an important antioxidant that plays a crucial role in the cellular protection against oxidative stress and detoxification of electrophilic mutagens, and carcinogens. Glutathione transferases are enzymes catalyzing glutathione-dependent reactions that lead to inactivation and conjugation of toxic compounds, processes followed by subsequent excretion of the detoxified products. Degeneration and loss of neuromelanin-containing dopaminergic neurons in the nigrostriatal neurons generally involves oxidative stress, neuroinflammation, alpha-synuclein aggregation to neurotoxic oligomers, mitochondrial dysfunction, protein degradation dysfunction, and endoplasmic reticulum stress. However, it is still unclear what triggers these neurodegenerative processes. It has been reported that aminochrome may elicit all of these mechanisms and, interestingly, aminochrome is formed inside neuromelanin-containing dopaminergic neurons during neuromelanin synthesis. Aminochrome is a neurotoxic ortho-quinone formed in neuromelanin synthesis. However, it seems paradoxical that the neurotoxin aminochrome is generated during neuromelanin synthesis, even though healthy seniors have these neurons intact when they die. The explanation of this paradox is the existence of protective tools against aminochrome neurotoxicity composed of the enzymes DT-diaphorase, expressed in these neurons, and glutathione transferase M2-2, expressed in astrocytes. Recently, it has been reported that dopaminergic neurons can be protected by glutathione transferase M2-2 from astrocytes, which secrete exosomes containing the protective enzyme.
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影响因子：
16.6
作者：
Cascella R;Chen SW;Bigi A;Camino JD;Xu CK;Dobson CM;Chiti F;Cremades N;Cecchi C
通讯作者：
Cecchi C
影响因子：
5.6
作者：
Asanuma M;Miyazaki I
通讯作者：
Miyazaki I
影响因子：
5.6
作者：
Franco R;Rivas-Santisteban R;Navarro G;Pinna A;Reyes-Resina I
通讯作者：
Reyes-Resina I
影响因子：
6.1
作者：
Arriagada, C;Paris, I;Segura-Aguilar, J
通讯作者：
Segura-Aguilar, J
影响因子：
3.4
作者：
de Araujo, Fillipe M.;Ferreir, Rafael S.;Silva, Victor Diogenes A.
通讯作者：
Silva, Victor Diogenes A.