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

• Published in: Scientific reports Vol. 3; no. 1; p. 1224
• Main Authors: Toba, Shiori, Tamura, Yasuhisa, Kumamoto, Kanako, Yamada, Masami, Takao, Keizo, Hattori, Satoko, Miyakawa, Tsuyoshi, Kataoka, Yosky, Azuma, Mitsuyoshi, Hayasaka, Kiyoshi, Amamoto, Masano, Tominaga, Keiko, Wynshaw-Boris, Anthony, Wanibuchi, Hideki, Oka, Yuichiro, Sato, Makoto, Kato, Mitsuhiro, Hirotsune, Shinji
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 06.02.2013; Nature Publishing Group
• Subjects: 1-Alkyl-2-acetylglycerophosphocholine Esterase - genetics; 1-Alkyl-2-acetylglycerophosphocholine Esterase - metabolism; 631/154/309/2144; 631/378/1689/2608; 631/378/340; 692/699/375/366; Administration, Oral; Animals; Blood-Brain Barrier - metabolism; Calpain; Calpain - antagonists & inhibitors; Calpain - metabolism; Carbamates - chemistry; Carbamates - pharmacology; Carbamates - therapeutic use; Cell Line; Cell migration; Fluorodeoxyglucose F18 - chemistry; Fluorodeoxyglucose F18 - metabolism; Glycoproteins - chemistry; Glycoproteins - pharmacology; Glycoproteins - therapeutic use; Humanities and Social Sciences; Humans; Lissencephaly; Lissencephaly - drug therapy; Lissencephaly - physiopathology; Lissencephaly - prevention & control; Male; Mice; Microtubule-Associated Proteins - genetics; Microtubule-Associated Proteins - metabolism; Motor Activity - drug effects; multidisciplinary; Nerve Growth Factor - metabolism; Neurons - metabolism; Positron-Emission Tomography; Receptors, GABA - metabolism; Retrograde transport; Rodents; Science
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep01224

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 18 F-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.