Brown D R
MRC Cambridge Centre for Brain Repair, England.
J Neurosci Res. 1998 Nov 1;54(3):331-40. doi: 10.1002/(SICI)1097-4547(19981101)54:3<331::AID-JNR4>3.0.CO;2-K.
A peptide fragment of the prion protein, PrP106-126 is toxic to neuronal cells in culture. This toxicity is dependent on neuronal expression of the prion protein (PrPc) and also the presence of microglia. The role of expression of the PrPc in neurotoxicity of this peptide was investigated using mice that overexpress the prion protein. Cells derived from two different strains of PrPc-overexpressing mice were used (Tg20 and Tg35). PrP106-126 was more toxic to Tg35 cerebellar cells than wild-type or Tg20 cells. This increased toxicity required the presence of microglia. Analysis of microglia derived from wild-type and PrPc-overexpressing cells showed that Tg35 microglia were more easily activated than wild-type microglia, were more easily stimulated to proliferate by astrocytes, and had a higher level of PrPc expression. This may explain the increased PrP106-126 toxicity to Tg35 PrPc-overexpressing cerebellar cells. These results suggest that the toxicity of PrP106-126 may depend on the level of expression of PrPc by microglia as well as by neurones.
朊病毒蛋白的一个肽片段PrP106 - 126对培养中的神经元细胞有毒性。这种毒性依赖于朊病毒蛋白（PrPc）的神经元表达以及小胶质细胞的存在。使用过度表达朊病毒蛋白的小鼠研究了PrPc表达在该肽神经毒性中的作用。使用了来自两种不同品系的过度表达PrPc的小鼠（Tg20和Tg35）的细胞。PrP106 - 126对Tg35小脑细胞的毒性比对野生型或Tg20细胞更强。这种增加的毒性需要小胶质细胞的存在。对来自野生型和过度表达PrPc的细胞的小胶质细胞分析表明，Tg35小胶质细胞比野生型小胶质细胞更容易被激活，更容易被星形胶质细胞刺激增殖，并且具有更高水平的PrPc表达。这可能解释了PrP106 - 126对Tg35过度表达PrPc的小脑细胞毒性增加的原因。这些结果表明，PrP106 - 126的毒性可能取决于小胶质细胞以及神经元中PrPc的表达水平。
