Abstract
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 ¹⁸F-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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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1-Alkyl-2-acetylglycerophosphocholine Esterase / genetics
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1-Alkyl-2-acetylglycerophosphocholine Esterase / metabolism
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Administration, Oral
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Animals
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Blood-Brain Barrier / metabolism*
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Calpain / antagonists & inhibitors*
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Calpain / metabolism
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Carbamates / chemistry
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Carbamates / pharmacology
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Carbamates / therapeutic use*
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Cell Line
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Fluorodeoxyglucose F18 / chemistry
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Fluorodeoxyglucose F18 / metabolism
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Glycoproteins / chemistry
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Glycoproteins / pharmacology
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Glycoproteins / therapeutic use*
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Humans
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Lissencephaly / drug therapy*
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Lissencephaly / physiopathology
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Lissencephaly / prevention & control
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Male
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Mice
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Microtubule-Associated Proteins / genetics
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Microtubule-Associated Proteins / metabolism
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Motor Activity / drug effects
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Nerve Growth Factor / metabolism
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Neurons / metabolism
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Positron-Emission Tomography
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Receptors, GABA / metabolism
Substances
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((1S)-1-((((1S)-1-benzyl-3-cyclopropylamino-2,3-di-oxopropyl)amino)carbonyl)-3-methylbutyl)carbamic acid 5-methoxy-3-oxapentyl ester
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Carbamates
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Glycoproteins
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Microtubule-Associated Proteins
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Receptors, GABA
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calpain inhibitors
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Fluorodeoxyglucose F18
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Nerve Growth Factor
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1-Alkyl-2-acetylglycerophosphocholine Esterase
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Pafah1b1 protein, mouse
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Calpain