Microglial AGE-albumin is critical for neuronal death in Parkinson's disease: a possible implication for theranostics.
Microglial AGE-albumin is critical for neuronal death in Parkinson's disease: a possible implication for theranostics.
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DOI：
10.2147/ijn.s95077
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发表时间：
2015
影响因子：
8
通讯作者：
Lee B
中科院分区：
文献类型：
--
作者：
Bayarsaikhan E;Bayarsaikhan D;Lee J;Son M;Oh S;Moon J;Park HJ;Roshini A;Kim SU;Song BJ;Jo SM;Byun K;Lee B
众所周知，晚期糖基化终末产物 (AGE) 通过诱导蛋白质聚集和交联、路易体形成和神经元死亡，在包括帕金森病 (PD) 在内的神经退行性疾病的发病机制中发挥重要作用。在这项研究中，我们观察到 AGE-白蛋白（人 PD 大脑中最丰富的 AGE 产物）在激活的小胶质细胞中合成，并在细胞外空间积聚。抗坏血酸和细胞松弛素处理明显抑制人激活小胶质细胞中的 AGE-白蛋白合成。累积的 AGE-白蛋白上调 AGE 受体，导致人类初级多巴胺 (DA) 神经元凋亡。在动物实验中，我们观察到通过可溶性 AGE 受体治疗可减少 DA 神经元细胞死亡。我们的研究提供的证据表明，活化的小胶质细胞是 AGE-白蛋白积累的主要贡献者之一，对人类和动物 PD 大脑中的 DA 神经元有害。最后，活化的小胶质细胞 AGE-白蛋白可用作对包括 PD 在内的神经退行性疾病具有高敏感性的诊断和治疗生物标志物。
Advanced glycation end products (AGEs) are known to play an important role in the pathogenesis of neurodegenerative diseases, including Parkinson’s disease (PD), by inducing protein aggregation and cross-link, formation of Lewy body, and neuronal death. In this study, we observed that AGE-albumin, the most abundant AGE product in the human PD brain, is synthesized in activated microglial cells and accumulates in the extracellular space. AGE-albumin synthesis in human-activated microglial cells is distinctly inhibited by ascorbic acid and cytochalasin treatment. Accumulated AGE-albumin upregulates the receptor to AGE, leading to apoptosis of human primary dopamine (DA) neurons. In animal experiments, we observed reduced DA neuronal cell death by treatment with soluble receptor to AGE. Our study provides evidence that activated microglial cells are one of the main contributors in AGE-albumin accumulation, deleterious to DA neurons in human and animal PD brains. Finally, activated microglial AGE-albumin could be used as a diagnostic and therapeutic biomarker with high sensitivity for neurodegenerative disorders, including PD.