Dipeptidyl compounds ameliorate the serumdeprivation-induced reduction in cell viability via the neurotrophin-activating effect in SH-SY5Y cells

Ken ichi Tanaka, Hiroya Ogo, Hiroaki Kaji, Kaori Miyatake, Erika Tokudome, Kanako Sonoda, Norio Ogawa, Masato Asanuma

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Objectives and methods: We have searched for low-molecular-weight compounds as potent new nonimmunosuppressive immunophilin ligands (NI-IPLs) that are stronger than existent NI-IPLs such as GPI1046 and/or V10367 from the perspective of neuroprotective efficacy. We selected six dipeptidyl compounds as new NI-IPL candidates, and first examined the effects of each of these compounds on the serum-deprivation-induced reduction in the viability of SH-SY5Y cells. In addition, we clarified the effects of these compounds on neurotrophin release into medium in SH-SY5Y cells. Results: Pre-treatment with Leu-Ile and Ile-Ile prevented the serum deprivation-induced reduction in cell viability in SH-SY5Y cells. In naive SH-SY5Y cells, treatment with Leu-Ile and Ile-Ile for 24 hours significantly increased both brain-derived neurotrophic factor and glial cell-line-derived neurotrophic factor releases in comparison with relative vehicle treatments. Moreover, none of the dipeptidyl compounds could prevent the concanavalin A-induced enhancement in interleukin-2 and interleukin-4 release in mouse spleen cells. Discussion: The immunosuppressive effect is not essential to the neuroprotective properties of dipeptidyl compounds, and Leu-Ile and Ile-Ile have neurotrophin-activating effects, like FK506 and its existing non-immunosuppressive derivatives.

Original languageEnglish
Pages (from-to)619-622
Number of pages4
JournalNeurological Research
Issue number6
Publication statusPublished - Jul 1 2012



  • Dipeptide
  • Leu-ile
  • Mmunophilin ligand
  • Neuroprotection
  • Neurotrophin

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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