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Sci Rep. 2017 Sep 21;7(1):12119. doi: 10.1038/s41598-017-12449-6.

Regulation of axonal regeneration by the level of function of the endogenous Nogo receptor antagonist LOTUS.

Author information

1
Molecular Medical Bioscience Laboratory, Yokohama City University Graduate School of Medical Life Science, Yokohama, 230-0045, Japan.
2
Cellular Neuroscience, Neurodegeneration and Repair Program, Departments of Neurology and Neuroscience, Yale University School of Medicine, New Haven, CT, 06536, USA.
3
Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine, Yokohama, 246-0004, Japan.
4
Department of Neuroanatomy, Yokohama City University Graduate School of Medicine, Yokohama, 246-0004, Japan.
5
Department of Neurosurgery, Yokohama City University Graduate School of Medicine, Yokohama, 246-0004, Japan.
6
Advanced Medical Research Center, Yokohama City University Graduate School of Medicine, Yokohama, 236-0004, Japan.
7
Molecular Medical Bioscience Laboratory, Yokohama City University Graduate School of Medical Life Science, Yokohama, 230-0045, Japan. kohtaro@yokohama-cu.ac.jp.
8
Advanced Medical Research Center, Yokohama City University Graduate School of Medicine, Yokohama, 236-0004, Japan. kohtaro@yokohama-cu.ac.jp.

Abstract

Axonal regeneration in the adult mammalian central nervous system is limited in part by the non-permissive environment, including axonal growth inhibitors such as the Nogo-A protein. How the functions of these inhibitors can be blocked remains unclear. Here, we examined the role of LOTUS, an endogenous Nogo receptor antagonist, in promoting functional recovery and neural repair after spinal cord injury (SCI), as well as axonal regeneration after optic nerve crush. Wild-type untreated mice show incomplete but substantial intrinsic motor recovery after SCI. The genetic deletion of LOTUS delays and decreases the extent of motor recovery, suggesting that LOTUS is required for spontaneous neural repair. The neuronal overexpression of LOTUS in transgenic mice promotes motor recovery after SCI, and recombinant viral overexpression of LOTUS enhances retinal ganglion cell axonal regeneration after optic nerve crush. Thus, the level of LOTUS function titrates axonal regeneration.

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