4.7 Article

Post-natal treatment by a blood-brain-barrier permeable calpain inhibitor, SNJ1945 rescued defective function in lissencephaly

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SCIENTIFIC REPORTS
卷 3, 期 -, 页码 -

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NATURE PUBLISHING GROUP
DOI: 10.1038/srep01224

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资金

  1. Ministry of Education, Science, Sports and Culture of Japan
  2. Knowledge Cluster Initiative (Stage-2) Research Foundation
  3. Takeda Science Foundation
  4. Sumitomo Foundation
  5. NIH [NS41030, HD47380]
  6. Japan Society for the Promotion of Science (JSPS) [22390056]
  7. Adaptable and Seamless Technology Transfer Program (A-STEP) through Target-driven R&D, Japan Science and Technology Agency [AS231Z02224G]
  8. Ministry of Education, Culture, Sports, Science and Technology (MEXT) [11001981]
  9. Uehara Memorial Foundation
  10. KAKENHI from the Ministry of Education, Science, Sports and Culture of Japan (MEXT) of Japan [16680015, 21300121, 21390069, 19653081]
  11. Neuroinformatics Japan Center (NIJC)
  12. CREST of Japan Science and Technology Agency (JST)
  13. Funding Program for Next Generation World-Leading Researchers (Next Program)
  14. Multidisciplinary program for elucidating the brain development from molecules to social behavior (Fukui Brain Project)
  15. Ministry of Education, Culture, Sports, Science and Technology of Japan
  16. Grants-in-Aid for Scientific Research [24111546, 24700352, 21390069, 21300121, 25460399, 22390056, 24113007, 23659092] Funding Source: KAKEN

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Toward a therapeutic intervention of lissencephaly, we applied a novel calpain inhibitor, SNJ1945. Peri-natal or post-natal treatment with SNJ1945 rescued defective neuronal migration in Lis1(+/-) mice, impaired behavioral performance and improvement of F-18-FDG uptake. Furthermore, SNJ1945 improved the neural circuit formation and retrograde transport of NFG in Lis1(+/-) mice. Thus, SNJ1945 is a potential drug for the treatment of human lissencephaly patients.

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