1. Academic Validation
  2. Inhibition of excitatory neuronal cell death by cell-permeable calcineurin autoinhibitory peptide

Inhibition of excitatory neuronal cell death by cell-permeable calcineurin autoinhibitory peptide

  • J Neurochem. 2003 Dec;87(5):1145-51. doi: 10.1046/j.1471-4159.2003.02098.x.
Hiroaki Terada 1 Masayuki Matsushita Yun-Fei Lu Takeshi Shirai Sheng-Tian Li Kazuhito Tomizawa Akiyoshi Moriwaki Shinsaku Nishio Isao Date Takashi Ohmoto Hideki Matsui
Affiliations

Affiliation

  • 1 Department of Physiology, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
Abstract

In glutamate-mediated excitatory neuronal cell death, immunosuppressants (FK506, Cys-A) are powerful agents that protect neurons from Apoptosis. Immunosuppressants inhibit two types of Enzyme, calcium/calmodulin-dependent protein Phosphatase (calcineurin: CaN), and peptidyl-prolyl cis-trans-isomerase (PPIase) activity such as the FKBP family. In this study, we used a protein transduction approach to determine the functional role of CaN and to produce a potential therapeutic agent for glutamate-mediated neuronal cell death. We created a novel cell-permeable CaN autoinhibitory peptide using the 11 arginine protein transduction domain. This peptide was highly efficient at transducing into primary culture neurons, potently inhibited CaN Phosphatase activities, and inhibited glutamate-mediated neuronal cell death. These results showed that CaN plays an important role in excitatory neuronal cell death and cell-permeable CaN autoinhibitory peptide could be a new drug to protect neurons from excitatory neuronal death.

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