Characterization of the precursor protein of the non-A beta component of senile plaques (NACP) in the human central nervous system
Characterization of the precursor protein of the non-A beta component of senile plaques (NACP) in the human central nervous system
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DOI：
10.1097/00005072-199608000-00004
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发表时间：
1996-08-01
影响因子：
3.2
通讯作者：
Hyman, BT
中科院分区：
文献类型：
--
作者：
Irizarry, MC;Kim, TW;Hyman, BT
一种新颖且高度保守的突触前蛋白已在啮齿类动物（突触核蛋白/SYN-1）、鸣禽（synelfin）和人类（老年斑非 A β 成分的前体蛋白，NACP）中被独立描述；在阿尔茨海默病（AD）的老年斑中检测到了后者的片段。我们表征了 NACP 在人类 AD 和非 AD 大脑中的表达。亚细胞分离研究表明 NACP 主要定位于人类颞叶皮层的胞质部分。在各种膜和囊泡部分中也可检测到 NACP，这表明该蛋白质与包括突触囊泡在内的膜结构相关。在新皮质和边缘区域观察到神经毡的细胞周免疫染色，支持突触定位。 AD 大脑中的老年斑没有免疫反应性，共聚焦显微镜表明核心斑块中 NACP 免疫反应性丧失。通过免疫印迹测量，AD 和对照额叶皮质中的蛋白质含量没有发现差异。 PCR 分析表明，全长 mRNA 产物是 AD 和对照人脑中的主要剪接形式。因此，尽管 NACP 的疏水片段与老年斑相关，但我们的数据表明前体本身并不是斑块的重要组成部分，并且 NACP 合成在 AD 中并未发生实质性改变。然而，该蛋白是 AD 中易于退化的突触区域的丰富成分，并且可能在疾病的表达或进展中发挥作用。
A novel and highly conserved presynaptic protein has been independently described in rodents (synuclein/SYN-1), songbirds (synelfin), and humans (the precursor protein of the non-A beta component of senile plaques, NACP); a fragment of the latter has been detected in senile plaques in Alzheimer's disease (AD). We characterized the expression of NACP in human AD and non-AD brain. A subcellular fractionation study demonstrated that NACP was mainly localized to cytosolic fractions of human temporal cortex. NACP was also detectable in various membrane and vesicular fractions, suggesting that the protein was associated with membrane structures including synaptic vesicles. Pericellular immunostaining of the neuropil was observed in neocortical and limbic regions, supporting a synaptic localization. Senile plaques in AD brains were not immunoreactive, and confocal microscopy suggested a loss of NACP immunoreactivity in cored plaques. No difference was found in the amount of protein in AD and control frontal cortex, as measured by immunoblotting. PCR analysis showed that the full-length mRNA product was the major splice form in both AD and control human brains. Thus, despite the association of a hydrophobic fragment of NACP with senile plaques, our data suggest that the precursor itself is not a significant component of plaques and NACP synthesis is not substantially altered in AD. Nevertheless, the protein is an abundant component of synaptic regions prone to degeneration in AD, and may have a role in the expression or advancement of the disease.