Phosphatidylinositol-glycan-phospholipase D is involved in neurodegeneration in prion disease.
Phosphatidylinositol-glycan-phospholipase D is involved in neurodegeneration in prion disease.
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磷脂酰肌醇 - 糖磷脂酶D参与病毒疾病的神经退行性。
DOI：
10.1371/journal.pone.0122120
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Kim YS
中科院分区：
文献类型：
--
作者：
Jin JK;Jang B;Jin HT;Choi EK;Jung CG;Akatsu H;Kim JI;Carp RI;Kim YS
PrPSc由正常的糖基磷脂酰肌醇（GPI）锚定朊病毒蛋白（PrPC）通过翻译后修饰形成。大多数GPI锚定蛋白已被证明是由GPI磷脂酶切割。最近，GPI-磷脂酶D（GPI-PLD）被证明是GPI锚的严格特异性酶。为了研究GPI-PLD在朊病毒疾病神经变性过程中的参与，我们检测了GPI-PLD在朊病毒动物模型（羊瘙痒病）大脑中的mRNA和蛋白表达水平，以及散发性和家族性克雅氏病（CJD）患者的大脑和脑脊液（CSF）中的表达水平。我们发现，与对照组相比，GPI-PLD的表达显着下调，在羊瘙痒症感染小鼠的大脑，特别是在小窝蛋白富集膜组分。有趣的是，观察到GPI-PLD表达水平的降低开始于PrPSc开始在感染的大脑中积累的同时，并且在CJD患者的大脑和CSF中也观察到这种降低;然而，在阿尔茨海默病患者的大脑或CSF样本中没有观察到表达差异。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朊病毒的传播。
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.
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影响因子：
3.1
作者：
Lewis, Victoria;Hooper, Nigel M.
通讯作者：
Hooper, Nigel M.
影响因子：
3.3
作者：
Han, JM;Kim, Y;Ryu, SH
通讯作者：
Ryu, SH
影响因子：
12.7
作者：
Choi, SI;Ju, WK;Kim, YS
通讯作者：
Kim, YS
影响因子：
2.2
作者：
MAGUIRE, GA;GOSSNER, A
通讯作者：
GOSSNER, A
DOI：
10.1083/jcb.129.3.619
发表时间：
1995-05
期刊：
The Journal of cell biology
影响因子：
--
作者：
Gorodinsky A;Harris DA
通讯作者：
Harris DA