"MOLECULAR MODE OF ACTION OF NEUROTROPHIC FACTOR,PROSAPOSIN"

鞘脂激活蛋白原是激活鞘脂水解酶的鞘脂激活蛋白的前体，已被鉴定为神经营养因子。鞘脂激活蛋白原对人神经母细胞瘤细胞、海马神经元和PC 12细胞的神经营养活性存在于鞘脂激活蛋白原C结构域的NH_2端亲水序列。最近研究表明，睾丸支持细胞脑内移植可促进6-羟基多巴胺诱导的偏侧帕金森病大鼠的功能恢复，体外实验表明，当胚胎神经元与大鼠支持细胞生长的培养基一起培养时，多巴胺能神经元的存活和生长增强。由于saposin原是支持细胞的主要分泌蛋白之一，其对多巴胺能神经元的营养作用是可以想象的。在这里，我们表明，肽包括18个氨基酸序列（18-mer肽; LSELIINNATEELLIKGL）位于NH_2-末端的亲水序列的大鼠saposin原的C-域促进生存和突起生长的酪氨酸羟化酶阳性神经元在胚胎15天大鼠腹侧中脑培养。

Prosaposin, the precursor of saposins which activate sphingolipid hydrolases, has been identified as a neurotrophic factor. The neurotrophic activity of prosaposin on human neuroblastoma cells, hippocampal neurons, and PC 12 cells has been shown to reside in the NH_2-terminal hydrophilic sequence of the C-domain of prosaposin. It has recently demonstrated that intracerebral transplantation of testis-derived sertoli cells promotes functional recovery in rats with 6-hydroxydopamine-induced hemiparkinsonism, and in vitro experiments demonstrated enhanced dopaminergic neuronal survival and outgrowth when embryonic neurons were cultured with medium in which rat Sertoli cells had been grown. Since prosaposin is one of the major Sertoli cell secretory proteins, its trophic effect on dopaminergic neurons is conceivable. Here we show that a peptide comprising the 18-amino-acid sequence (18-mer peptide ; LSELIINNATEELLIKGL) located in the NH_2-terminal hydrophilic sequence of the C-domain of rat prosaposin promoted survival and neurite outgrowth of tyrosine hydroxylase-positive neurons on embryonic day 15 rat ventral mesencephalic cultures.