Human brain nucleoside diphosphate kinase activity is decreased in Alzheimer's disease and Down syndrome.
Human brain nucleoside diphosphate kinase activity is decreased in Alzheimer's disease and Down syndrome.
复制标题
阿尔茨海默病和唐氏综合症中人脑核苷二磷酸激酶活性降低。
DOI：
10.1016/s0006-291x(02)02035-1
复制
发表时间：
2002
影响因子：
3.1
通讯作者：
G. Lubec
中科院分区：
文献类型：
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作者：
Seong Hwan Kim;M. Fountoulakis;N. Cairns;G. Lubec
在大脑中，核苷二磷酸激酶(NDPK)及其编码基因nm23参与调节神经细胞的增殖、分化和突起生长。然而，NDPK在神经退行性疾病中的作用尚未见报道。利用蛋白质组学技术，我们评估了表现出AD样神经病理的阿尔茨海默病(AD)和唐氏综合征(DS)患者七个脑区NDPK-A的蛋白水平。在这两种疾病的脑区(额叶、枕叶和顶叶皮质)，NDPK-A显著降低。由于脑组织样本的限制，我们测量了三个脑区(额叶皮质、颞叶皮质和小脑)的NDPK活性。额叶皮质(AD)和额叶和颞叶皮质(DS)NDPK比活性显著降低。由于NDPK-B也可以驱动NDPK的活性，因此采用Western印迹方法研究了额叶皮质中NDPK-A和NDPK-B的蛋白表达水平。NDPK-A在AD时显著降低，这与蛋白质组学结果一致。DS组和AD组NDPK-A表达水平略有下降，NDPK-B蛋白表达水平均呈中度下降，但无统计学意义。我们认为，NDPK的氧化修饰可以导致NDPK活性降低，从而通过多种机制影响神经退行性疾病中作为多功能酶的几个神经元功能。
In brain, nucleoside diphosphate kinase (NDPK) and its coding gene, nm23, have been implicated to modulate neuronal cell proliferation, differentiation, and neurite outgrowth. However, a role of NDPK in neurodegenerative diseases has not been reported yet. Using proteomics techniques, we evaluated the protein levels of NDPK-A in seven brain regions from patients with Alzheimer's disease (AD) and Down syndrome (DS) showing AD-like neuropathology. NDPK-A was significantly decreased in brain regions (frontal, occipital, and parietal cortices) of both disorders. Due to the limitation of brain samples, the activity of NDPK was measured in three brain regions (frontal cortex, temporal cortex, and cerebellum). The specific activity of NDPK was significantly decreased in AD (frontal cortex) and DS (frontal and temporal cortices). Since NDPK-B could also drive the activity of NDPK, protein expression levels of both NDPK-A and NDPK-B were studied in frontal cortex by Western blot analysis. NDPK-A was significantly decreased in AD, which was consistent with the results of proteomics. However, NDPK-A was slightly decreased in DS and protein expression levels of NDPK-B in both DS and AD were moderately decreased, without reaching statistical significance. We propose that oxidative modification of NDPK could lead to the decreased activity of NDPK and, subsequently, influence several neuronal functions in neurodegenerative diseases as multifunctional enzyme through several mechanisms.
Ishijima Y. 等人：“核苷二磷酸激酶的过度表达会诱导神经突生长，其替换为非活性形式会导致 PC12D 细胞中神经生长因子和二丁酰环 AMP 诱导效应的抑制”FEBS Lett.. 445. 1
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