Minami Akira
Department of Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka.
Yakugaku Zasshi. 2015;135(12):1341-8. doi: 10.1248/yakushi.15-00220.
Sialidase removes sialic acid residues from sialoglycoconjugates such as glycoproteins and glycolipids. Since sialic acid plays crucial roles in synaptic plasticity and memory in the hippocampus, the regulation of sialyl signaling by sialidase is also necessary for neural functions. However, since mammalian sialidase activity is remarkably weak, it has been difficult to detect sialidase activity in mammalian tissues. Determination of the distribution of sialidase activity in living mammalian tissues would provide much valuable information for understanding the roles of sialidase in physiological functions. Therefore, we synthesized a novel benzothiazolylphenol-based sialic acid derivative (BTP-Neu5Ac) as a fluorescent sialidase substrate. After cleavage of BTP-Neu5Ac, which is water soluble and shows little fluorescence, with sialidase, the water-insoluble fluorophore benzothiazolylphenol (BTP) released from BTP-Neu5Ac stains tissue and shows bright fluorescence. BTP-Neu5Ac can visualize sialidase activity in brain tissue with high levels of sensitivity and specificity. The sialidase expression level is markedly high in various human cancers such as colon, renal, prostate, and ovarian cancers. BTP-Neu5Ac can detect human colon cancers sensitively. Thus, BTP-Neu5Ac is useful not only for physiological research but also as a cancer probe. BTP-Neu5Ac is now being used in virology research. In this review, methods for histochemical imaging of sialidase activity and the role of sialidase in hippocampal memory are described based on the author's study of multidimensional analysis of hippocampal excitatory neurotransmission and development of analytical tools for glycans, which was awarded a prize by the Tokai branch of the Pharmaceutical Society of Japan.
唾液酸酶可从糖蛋白和糖脂等唾液酸糖缀合物中去除唾液酸残基。由于唾液酸在海马体的突触可塑性和记忆中起着关键作用，唾液酸酶对唾液酸信号的调节对于神经功能也是必需的。然而，由于哺乳动物唾液酸酶活性非常弱，在哺乳动物组织中检测唾液酸酶活性一直很困难。确定唾液酸酶活性在活体哺乳动物组织中的分布，将为理解唾液酸酶在生理功能中的作用提供许多有价值的信息。因此，我们合成了一种新型的基于苯并噻唑基苯酚的唾液酸衍生物（BTP-Neu5Ac）作为荧光唾液酸酶底物。BTP-Neu5Ac是水溶性的，荧光很弱，在被唾液酸酶切割后，从BTP-Neu5Ac释放出的水不溶性荧光团苯并噻唑基苯酚（BTP）会对组织进行染色并发出明亮的荧光。BTP-Neu5Ac能够以高灵敏度和特异性可视化脑组织中的唾液酸酶活性。在结肠癌、肾癌、前列腺癌和卵巢癌等多种人类癌症中，唾液酸酶的表达水平明显较高。BTP-Neu5Ac能够灵敏地检测人类结肠癌。因此，BTP-Neu5Ac不仅对生理学研究有用，而且还可作为一种癌症探针。BTP-Neu5Ac目前正在用于病毒学研究。在这篇综述中，基于作者对海马体兴奋性神经传递的多维分析以及聚糖分析工具的开发（该研究获得了日本药学会东海分会的奖项），描述了唾液酸酶活性的组织化学成像方法以及唾液酸酶在海马体记忆中的作用。
