Brown D R, Kretzschmar H A
Department of Neuropathology, University of Göttingen, Germany.
Histol Histopathol. 1997 Jul;12(3):883-92.
Prion diseases are characterized by the accumulation of PrPSc, an altered isoform of a normal cellular protein, PrPc. The prion hypothesis holds that the process of conformational change from PrPc to PrPSc under the influence of PrPSc constitutes the basic infectious mechanism in prion diseases. It is still unknown whether pathological changes in these diseases, which include spongiform degeneration, nerve cell loss and gliosis, are the result of neurotoxicity of PrPSc, loss of function of PrPc or some other mechanism. Recent in vitro findings using a synthetic peptide of human PrPc implicate microglia as a mediator of pathological changes. The mechanism of the toxicity of this peptide involves activation of microglia oxidative stress, and direct interactions with PrPc-synthesizing neurones that reduce their ability to cope with oxidative stress. Microglia thus seem to emerge as a mediator of neuronal degeneration and cell death in prion diseases.
朊病毒疾病的特征是异常形式的正常细胞蛋白PrPSc的积累，PrPSc由正常细胞蛋白PrPc转变而来。朊病毒假说认为，在PrPSc的影响下，PrPc向PrPSc的构象变化过程构成了朊病毒疾病的基本感染机制。这些疾病中的病理变化，包括海绵状变性、神经细胞丢失和胶质细胞增生，究竟是PrPSc的神经毒性、PrPc功能丧失还是其他机制导致的，目前仍不清楚。最近使用人PrPc合成肽的体外研究结果表明，小胶质细胞是病理变化的介导者。该肽的毒性机制涉及激活小胶质细胞氧化应激，并与合成PrPc的神经元直接相互作用，从而降低其应对氧化应激的能力。因此，小胶质细胞似乎成为了朊病毒疾病中神经元变性和细胞死亡的介导者。
