Jin Jae-Kwang, Jang Byungki, Jin Hyoung Tae, Choi Eun-Kyoung, Jung Cha-Gyun, Akatsu Hiroyasu, Kim Jae-Il, Carp Richard I, Kim Yong-Sun
Ilsong Institute of Life Science, Hallym University, Anyang, Gyeonggi-do 431-060, Korea.
Department of Neurophysiology and Brain Science, Nagoya City University Graduate, School of Medical Sciences, Nagoya, Aichi 467-8601, Japan.
PLoS One. 2015 Apr 13;10(4):e0122120. doi: 10.1371/journal.pone.0122120. eCollection 2015.
PrPSc is formed from a normal glycosylphosphatidylinositol (GPI)-anchored prion protein (PrPC) by a posttranslational modification. Most GPI-anchored proteins have been shown to be cleaved by GPI phospholipases. Recently, GPI-phospholipase D (GPI-PLD) was shown to be a strictly specific enzyme for GPI anchors. To investigate the involvement of GPI-PLD in the processes of neurodegeneration in prion diseases, we examined the mRNA and protein expression levels of GPI-PLD in the brains of a prion animal model (scrapie), and in both the brains and cerebrospinal fluids (CSF) of sporadic and familial Creutzfeldt-Jakob disease (CJD) patients. We found that compared with controls, the expression of GPI-PLD was dramatically down-regulated in the brains of scrapie-infected mice, especially in the caveolin-enriched membrane fractions. Interestingly, the observed decrease in GPI-PLD expression levels began at the same time that PrPSc began to accumulate in the infected brains and this decrease was also observed in both the brain and CSF of CJD patients; however, no differences in expression were observed in either the brains or CSF specimens from Alzheimer's disease patients. Taken together, these results suggest that the down-regulation of GPI-PLD protein may be involved in prion propagation in the brains of prion diseases.
朊病毒蛋白（PrPSc）由正常的糖基磷脂酰肌醇（GPI）锚定的朊病毒蛋白（PrPC）经翻译后修饰形成。大多数GPI锚定蛋白已被证明可被GPI磷脂酶切割。最近，GPI磷脂酶D（GPI-PLD）被证明是一种对GPI锚具有严格特异性的酶。为了研究GPI-PLD在朊病毒疾病神经退行性变过程中的作用，我们检测了朊病毒动物模型（羊瘙痒病）脑内以及散发性和家族性克雅氏病（CJD）患者脑和脑脊液（CSF）中GPI-PLD的mRNA和蛋白表达水平。我们发现，与对照组相比，GPI-PLD在羊瘙痒病感染小鼠脑内的表达显著下调，尤其是在富含小窝蛋白的膜组分中。有趣的是，观察到GPI-PLD表达水平的下降与PrPSc开始在感染脑内积累的时间相同，并且在CJD患者的脑和CSF中也观察到了这种下降；然而，在阿尔茨海默病患者的脑或CSF标本中未观察到表达差异。综上所述，这些结果表明GPI-PLD蛋白的下调可能参与了朊病毒疾病脑内的朊病毒传播。
