It was previously reported that prosaposin possesses neurotrophic activity that is ascribed to an 18-mer
peptide comprising the hydrophilic sequence of the rat
saposin C domain. To evaluate the effect of the 18-mer
peptide on ischemic neuronal damage, the
peptide was infused in the left lateral ventricle immediately after occlusion of the left middle cerebral artery (MCA) in
stroke-prone spontaneously hypertensive (SP-SH) rats. The treatment ameliorated the
ischemia-induced space navigation disability and cortical
infarction and prevented secondary thalamic degeneration in a dose-dependent manner. In culture experiments, treatment with the 18-mer
peptide attenuated
free radical-induced neuronal injury at low concentrations (0.002 to 2 pg/mL), and the
peptide at higher concentrations (0.2 to 20 ng/mL) protected neurons against hypoxic insult. Furthermore, a
saposin C fragment comprising the 18-mer
peptide bound to synaptosomal fractions of the cerebral cortex, and this binding decreased at the 1st day after MCA occlusion and recovered to the preischemic level at the 7th day after
ischemia. These findings suggest that the 18-mer
peptide ameliorates neuronal damage in vivo and in vitro through binding to the functional receptor, although the
cDNA encoding
prosaposin receptor has not been determined yet.