Lack of permissive mechanisms and abundance of inhibitory molecules in the lesioned central nervous system of adult mammals contribute to the failure of functional recovery, which leads to severe disabilities in motor functions or pain. Previous studies have indicated that the neural cell adhesion molecule L1 constitutes a viable target to promote regeneration. In the present study, we describe the cloning, functional expression in Escherichia coli cells and purification of a recombinant αL1 Fab fragment that binds to L1 with comparable activity as the function-triggering monoclonal antibody 557.B6 and induces neurite outgrowth and neuronal survival in cultured neurons, despite its monovalent function. Infusion of αL1 Fab into the lesioned spinal cord of mice enhanced functional recovery after thoracic spinal cord compression injury. αL1 Fab treatment resulted in reduced scar volume, enhanced number of tyrosine hydroxylase-positive axons and increased linear density of VGLUT1 (vesicular glutamate transporter 1) on motoneurons. Furthermore, the number and soma size of ChAT (choline acetyltransferase)-positive motoneurons and the linear density of ChAT-positive boutons on motoneurons as well as parvalbumin-positive interneurons in the lumbar spinal cord were elevated. Stimulation of endogenous L1 by application of the αL1 Fab opens new avenues for recombinant antibody technology, offering prospects for therapeutic applications after traumatic nervous system lesions.
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Research Article|
May 29 2014
A Fab fragment directed against the neural cell adhesion molecule L1 enhances functional recovery after injury of the adult mouse spinal cord
Gabriele Loers;
Gabriele Loers
*Institut für Biosynthese Neuraler Strukturen, Zentrum für Molekulare Neurobiologie Hamburg, Universitätsklinikum-Hamburg Eppendorf, Hamburg, Germany
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Yi-Fang Cui;
Yi-Fang Cui
*Institut für Biosynthese Neuraler Strukturen, Zentrum für Molekulare Neurobiologie Hamburg, Universitätsklinikum-Hamburg Eppendorf, Hamburg, Germany
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Irmgard Neumaier;
Irmgard Neumaier
†Munich Center for Integrated Protein Science (CiPS-M) and Lehrstuhl für Biologische Chemie, Technische Universität München, Freising-Weihenstephan, Germany
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Melitta Schachner;
Melitta Schachner
1
*Institut für Biosynthese Neuraler Strukturen, Zentrum für Molekulare Neurobiologie Hamburg, Universitätsklinikum-Hamburg Eppendorf, Hamburg, Germany
‡Keck Center for Collaborative Neuroscience and Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ 08854, U.S.A.
1To whom correspondence should be addressed (email Melitta.Schachner@zmnh.uni-hamburg.de).
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Arne Skerra
Arne Skerra
†Munich Center for Integrated Protein Science (CiPS-M) and Lehrstuhl für Biologische Chemie, Technische Universität München, Freising-Weihenstephan, Germany
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Publisher: Portland Press Ltd
Received:
January 07 2014
Revision Received:
March 20 2014
Accepted:
March 27 2014
Accepted Manuscript online:
March 27 2014
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2014 Biochemical Society
2014
Biochem J (2014) 460 (3): 437–446.
Article history
Received:
January 07 2014
Revision Received:
March 20 2014
Accepted:
March 27 2014
Accepted Manuscript online:
March 27 2014
Citation
Gabriele Loers, Yi-Fang Cui, Irmgard Neumaier, Melitta Schachner, Arne Skerra; A Fab fragment directed against the neural cell adhesion molecule L1 enhances functional recovery after injury of the adult mouse spinal cord. Biochem J 15 June 2014; 460 (3): 437–446. doi: https://doi.org/10.1042/BJ20131677
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