"MOLECULAR MODE OF ACTION OF NEUROTROPHIC FACTOR,PROSAPOSIN"

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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.