A hydrophilic peptide comprising 18 amino acid residues of the prosaposin sequence has neurotrophic activity in vitro and in vivo.
Prosaposin, a 517-amino-acid glycoprotein, not only acts as the precursor of saposin A, B, C, and D but also possesses neurotrophic activity to rescue hippocampal CA1 neurons from ischemic damage in vivo and to promote neurite extension of neuroblastoma cells in vitro. Recently, the trophic activity of prosaposin on human neuroblastoma cells has been shown to reside in the NH2-terminal hydrophilic sequence (LIDNNRTEEILY) of the human saposin C. Here we show that prosaposin, saposin C, and a peptide comprising the 18-amino-acid sequence (18-mer peptide; LSELIINNATEELLIKGL) located in the NH2-terminal hydrophilic sequence of the rat saposin C-domain promoted survival and neurite outgrowth of cultured rat hippocampal neurons in a dose-dependent manner. Moreover, infusion for 7 days of the 18-mer peptide into the lateral ventricle of gerbils, starting either 2 h before or immediately after 3 min of forebrain ischemia, protected ischemia-induced learning disability and hippocampal CA1 neuronal loss. Thus, we ascribe the in vitro and in vivo trophic actions of prosaposin on hippocampal neurons to the linear 18-mer sequence and raise the possibility that this peptide can be used as an agent for the treatment of forebrain ischemic damage.
Kotani
Y
Y
Department of Neuropsychiatry, Ehime University School of Medicine, Japan.
Matsuda
S
S
Wen
T C
TC
Sakanaka
M
M
Tanaka
J
J
Maeda
N
N
Kondoh
K
K
Ueno
S
S
Sano
A
A
D000595:Amino Acid Sequence; D000818:Animals; D001362:Avoidance Learning; D002545:Brain Ischemia / Q000150:complications / Q000523:psychology; D002478:Cells, Cultured; D005849:Gerbillinae; D006023:Glycoproteins / Q000737:chemistry / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects; D007859:Learning Disabilities / Q000517:prevention & control; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D049231:Saposins; D049128:Sphingolipid Activator Proteins
D006023:Glycoproteins; D009414:Nerve Growth Factors; C483345:PSAP protein, human; D010446:Peptide Fragments; C483347:Psap protein, rat; D049231:Saposins; D049128:Sphingolipid Activator Proteins