Hydrophobic dipeptide Leu-Ile protects against neuronal death by inducing brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor synthesis

✍ Scribed by Atsumi Nitta; Hirofumi Nishioka; Hidefumi Fukumitsu; Yoshiko Furukawa; Haruo Sugiura; Liya Shen; Shoei Furukawa

• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: English
• Weight: 189 KB
• Volume: 78
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/jnr.20258

✦ Synopsis

Abstract

We investigated whether certain hydrophobic dipeptides, Leu‐Ile, Leu‐Pro, and Pro‐Ile, which partially resemble the site on FK506 that binds to immunophilin, could stimulate glial cell line‐derived neurotrophic factor (GDNF) and brain‐derived neurotrophic factor (BDNF) synthesis in cultured neurons and found only Leu‐Ile to be an active dipeptide. Leu‐Ile protected against the death of mesencephalic neurons from wild‐type mice but not from mice lacking the BDNF or GDNF gene. Next, we examined the effects of i.p. or i.c.v. administration of Leu‐Ile on BDNF and GDNF contents. Both types of administration increased the contents of BDNF and GDNF in the striatum of mice. Also, peripheral administration of Leu‐Ile inhibited dopaminergic (DA) denervation caused by unilateral injection of 6‐hydroxydopamine (6‐OHDA) into the striatum of mice. The number of rotations following a methamphetamine challenge was lower in the Leu‐Ile‐treated group than in the nontreated group. Next, we compared the calcineurin activity and immunosuppressant activity of Leu‐Ile with those of FK506. Leu‐Ile was not inhibitory toward calcineurin cellular activity in cultured neuronal cells. Furthermore, Leu‐Ile did not suppress concanavalin A (ConA)‐induced synthesis/secretion of interleukin‐2 by cultured spleen cells, suggesting that the immunosuppressant activity of Leu‐Ile may be negligible when used as a therapeutic tool for neurodegenerative diseases. © 2004 Wiley‐Liss, Inc.