Physiological role of NACP,the precursor of non-Abeta component of Alzheimer's disease amyloid

我们发现了阿尔茨海默病(AD)淀粉样蛋白中一种未知的成分，命名为NAC(Non-Abeta Component of AD淀粉样蛋白)，并克隆了编码NAC前体蛋白的cDNA，NACP.NACP后来被证明是鱼雷突触核蛋白的人类同源物，因此也被称为α-突触核蛋白。NACP是一种突触前蛋白，与PNP14或β-突触核蛋白组成一个基因家族。特别需要注意的是，NACP的表达模式反映了典型AD病理的分布。我们发现NACP不仅在AD脑内的突触区域有异常表达，而且在营养不良的突起中也有异常表达。因此，了解NACP的生理作用对于阐明AD脑内的病理生理事件至关重要。我们利用已建立的神经细胞系PC12进行研究，并通过RT-PCR鉴定了NACP家族蛋白β-突触核蛋白。我们提出了针对β-突触核蛋白的特异性抗体。同时，我们在缺血脑的海马区发现了NACP阳性的异常结构，并观察到神经元死亡。这一发现表明，NACP的改变可能以类似的方式参与了几种神经退行性疾病以及AD。

We found an unrecognized component of Alzheimer's disease (AD) amyloid, named NAC (non-Abeta component of AD amyloid) and cloned cDNA encoding NAC precursor protein, NACP.NACP is turned out to be human homologue of Torpedo synuclein, thus also called alpha-synuclein, later. NACP is a presynaptic protein, and constitutes a gene family with PNP14, or beta-synuclein. It should be particularly noted that expression pattern-for NACP mirrors the distribution of typical AD pathology. We showed that NACP is aberrantly expressed not only in synaptic region, but also in dystrophic neurites in AD brain. Thus, understanding the physiological role of NACP is crucial to clarify the pathophysiological events in AD brain.We utilized an established neuronal cell line, PC12 for this study, and identified a NACP family protein, beta-synuclein with RT-PCR.We have raised specific antibodies against beta-synuclein. Meanwhile, we have found NACP-positive abnormal structures in hippocampus of ischemia brain where neuronal death is observed. This finding suggests that alteration of NACP might be involved in a similar manner in several neurodegenerative diseases, as well as AD.