Microglia and Prion disease
Microglia and Prion disease
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DOI：
10.1002/jemt.1122
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发表时间：
2001-07-15
影响因子：
2.5
通讯作者：
Brown, DR
中科院分区：
文献类型：
--
作者：
Brown, DR
神经胶质增生是朊病毒疾病的特征之一。朊病毒病是一种低发病率的致命性神经退行性疾病，其著名的假说是一种蛋白质在不涉及核酸的情况下作为传染剂，以及一种牛的疾病BSE通过摄入朊病毒感染的牛肉而传播给人类的推测性想法。尽管有这些未经证实的假说，朊病毒疾病的病因仍然没有解决。这种疾病的快速退化过程之前有很长的潜伏期，几乎没有症状。疾病中的快速神经变性是由于正常神经元蛋白的异常同种型的沉积增加。与这种异常蛋白质的出现相关的是大量小胶质细胞的激活。对异常朊病毒蛋白和肽模拟物的细胞培养研究表明，神经元变性的发生是由于两种并发效应。首先，神经元对毒性损伤的抵抗力降低，其次，小胶质细胞产生的毒性物质（如活性氧）增加，星形胶质细胞的谷氨酸清除率降低。由异常形式的朊病毒蛋白激活的小胶质细胞也释放细胞因子，其刺激星形胶质细胞的变化，如增殖。这意味着小胶质细胞可能在启动朊病毒病的病理变化中起主要作用。本文综述了小胶质细胞在这些变化中的作用。(C)2001 Wiley-Liss，Inc.
Gliosis is one of the hallmarks of the prion diseases. Prion diseases are fatal neurodegenerative conditions of low incidence made famous by both the hypothesis that a protein acts as the infectious agent without involvement of nucleic acid and the speculative idea that a disease of cattle, BSE, has spread to humans from the ingestion of prion-infected beef. Despite these unproved hypotheses, the aetiology of the prion diseases remains unsolved. The rapid degenerative course of the disease is preceded by a long incubation period with little or no symptoms. The rapid neurodegeneration in the disease follows from increased deposition of an abnormal isoform of a normal neuronal protein. Go-incident with the appearance of this abnormal protein is the activation of large numbers of microglia. Studies in cell culture with both the abnormal prion protein and a peptide-mimic suggest that neuronal degeneration occurs because of two concurrent effects. First, there is a reduction in neuronal resistance to toxic insults and, second, there is an increase in the production of toxic substances such as reactive oxygen species by microglia and a decrease in glutamate clearance by astrocytes. Microglia activated by the abnormal form of the prion protein also release cytokines, which stimulate changes in astrocytes such as proliferation. The implication of this is that microglia may play a major role in initiating the pathological changes in prion disease. This review discusses the role of microglia in these changes. (C) 2001 Wiley-Liss, Inc.