Misasi Roberta, Hozumi Isao, Inuzuka Takashi, Capozzi Antonella, Mattei Vincenzo, Kuramoto Yukako, Shimeno Hiroshi, Soeda Shinji, Azuma Norihiro, Yamauchi Toyoaki, Hiraiwa Masao
Department of Geriatric and Neurology, Gifu University, School of Medicine, Gifu, Japan.
Cent Nerv Syst Agents Med Chem. 2009 Jun;9(2):119-31. doi: 10.2174/187152409788452045.
Prosaposin, a 66 kDa glycoprotein, was identified initially as the precursor of the sphingolipid activator proteins, saposins A-D, which are required for the enzymatic hydrolysis of certain sphingolipids by lysosomal hydrolases. While mature saposins are distributed to lysosomes, prosaposin exists in secretory body fluids and plasma membranes. In addition to its role as the precursor, prosaposin shows a variety of neurotrophic and myelinotrophic activities through a receptor-mediated mechanism. In studies in vivo, prosaposin was demonstrated to exert a variety of neuro-efficacies capable of preventing neuro-degeneration following neuro-injury and promoting the amelioration of allodynia and hyperalgesia in pain models. Collective findings indicate that prosaposin is not a simple house-keeping precursor protein; instead, it is a protein essentially required for the development and maintenance of the central and peripheral nervous systems. Accumulating evidence over the last decade has attracted interests in exploring and developing new therapeutic approaches using prosaposin for human disorders associated with neuro-degeneration. In this review we detail the structure characteristics, cell biological feature, in vivo efficacy, and neuro-therapeutic potential of prosaposin, thereby providing future prospective in clinical application of this multifunctional protein.
prosaposin是一种66 kDa的糖蛋白，最初被鉴定为鞘脂激活蛋白（saposins A-D）的前体，而鞘脂激活蛋白是溶酶体水解酶对某些鞘脂进行酶促水解所必需的。虽然成熟的鞘脂激活蛋白分布于溶酶体，但prosaposin存在于分泌体液和质膜中。除了作为前体的作用外，prosaposin还通过受体介导的机制表现出多种神经营养和髓鞘营养活性。在体内研究中，prosaposin被证明具有多种神经效应，能够预防神经损伤后的神经变性，并促进疼痛模型中异常性疼痛和痛觉过敏的改善。综合研究结果表明，prosaposin不是一种简单的管家前体蛋白；相反，它是中枢和外周神经系统发育和维持所必需的一种蛋白。过去十年中积累的证据引发了人们对探索和开发使用prosaposin治疗与神经变性相关人类疾病的新治疗方法的兴趣。在这篇综述中，我们详细阐述了prosaposin的结构特征、细胞生物学特性、体内疗效和神经治疗潜力，从而为这种多功能蛋白的临床应用提供未来展望。
