Mitsui Shinichi, Okui Akira, Uemura Hidetoshi, Mizuno Toshiki, Yamada Tatsuo, Yamamura Yoshio, Yamaguchi Nozomi
Department of Cell Biology, Research Institute for Geriatrics, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kyoto 602-8566, Japan.
Ann N Y Acad Sci. 2002 Nov;977:216-23. doi: 10.1111/j.1749-6632.2002.tb04818.x.
Neurosin is a kallikrein-like serine protease expressed preferentially in the human brain. It is localized in senile plaques and neurofibrillary tangles in the brains of individuals with Alzheimer's disease (AD) and in Lewy bodies in patients with Parkinson's disease. Neurosin is present in the cerebrospinal fluid (CSF) as a proenzyme and does not show any enzymatic activity. We have developed a sandwich ELISA system using monoclonal and polyclonal antibodies against human neurosin and have measured neurosin levels in the CSF from AD and non-CNS disease patients. Both male and female patients with peripheral neuropathy showed statistically positive correlations between CSF neurosin concentrations and age (males, n = 52, r = 0.482, p < 0.005; females, n = 43, r = 0.365, p < 0.005). In contrast, such positive correlation was not observed in the CSF from patients with AD. Further, some such patients showed extremely low levels of CSF neurosin. Our results suggest that neurosin is an aging-related protease and that a decreased CSF concentration of neurosin may be a risk factor for developing AD.
神经丝氨酸蛋白酶是一种类激肽释放酶的丝氨酸蛋白酶，在人类大脑中优先表达。它定位于阿尔茨海默病（AD）患者大脑中的老年斑和神经原纤维缠结以及帕金森病患者的路易小体中。神经丝氨酸蛋白酶以酶原形式存在于脑脊液（CSF）中，不显示任何酶活性。我们利用抗人神经丝氨酸蛋白酶的单克隆抗体和多克隆抗体开发了一种夹心酶联免疫吸附测定（ELISA）系统，并测定了AD患者和非中枢神经系统疾病患者脑脊液中的神经丝氨酸蛋白酶水平。患有周围神经病变的男性和女性患者脑脊液中神经丝氨酸蛋白酶浓度与年龄之间均存在统计学上的正相关（男性，n = 52，r = 0.482，p < 0.005；女性，n = 43，r = 0.365，p < 0.005）。相比之下，在AD患者的脑脊液中未观察到这种正相关。此外，一些此类患者脑脊液中的神经丝氨酸蛋白酶水平极低。我们的结果表明，神经丝氨酸蛋白酶是一种与衰老相关的蛋白酶，脑脊液中神经丝氨酸蛋白酶浓度降低可能是发生AD的一个危险因素。
