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

Journal of Neuroscience Research
Atsumi NittaShoei Furukawa

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 synt...Continue Reading

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Citations

Sep 17, 2008·Applied Microbiology and Biotechnology·Makoto Yagasaki, Shin-ichi Hashimoto
Jan 13, 2006·The Pharmacogenomics Journal·F FumagalliM A Riva
Jan 13, 2009·Pharmacology & Therapeutics·Sebastien Carnicella, Dorit Ron
Oct 1, 2008·Progress in Neurobiology·Ana SaavedraEmília P Duarte
Jan 1, 2008·Journal of Neuroimmunology·Jun KawanokuchiAkio Suzumura
Aug 24, 2012·The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology·Hyun-E LeeDong-Seok Kim

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