Soluble Cell Adhesion Molecule L1-Fc Promotes Locomotor Recovery in Rats after Spinal Cord Injury

Roonprapunt, Chanland; Huang, Wen Cheng; Grill, Raymond J.; Friedlander, David R.; Grumet, Martin; Chen, Suzhen; Schachner, Melitta; Young, Wise

doi:10.1089/089771503322385809

Cited by 100 publications

(81 citation statements)

References 61 publications

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“…it is downregulated on myelinated axons and re-expressed in regenerating axons after spinal cord injury [64,65] . Exogenous L1CAM is beneficial in promoting axon growth and functional recovery after spinal cord injury [66] and optic nerve lesion [67] and is involved in the regenerative growth of Purkinje cell axons in vivo [68] .…”

Section: Cell Adhesion Moleculesmentioning

confidence: 99%

Promoting remyelination for the treatment of multiple sclerosis: opportunities and challenges

Zhang

Guo

2013

Neurosci. Bull.

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Multiple sclerosis (MS) is a chronic and devastating autoimmune demyelinating disease of the central nervous system. With the increased understanding of the pathophysiology of this disease in the past two decades, many disease-modifying therapies that primarily target adaptive immunity have been shown to prevent exacerbations and new lesions in patients with relapsing-remitting MS. However, these therapies only have limited efficacy on the progression of disability. Increasing evidence has pointed to innate immunity, axonal damage and neuronal loss as important contributors to disease progression. Remyelination of denuded axons is considered an effective way to protect neurons from damage and to restore neuronal function. The identification of several key molecules and pathways controlling the differentiation of oligodendrocyte progenitor cells and myelination has yielded clues for the development of drug candidates that directly target remyelination and neuroprotection. The long-term efficacy of this strategy remains to be evaluated in clinical trials. Here, we provide an overview of current and emerging therapeutic concepts, with a focus on the opportunities and challenges for the remyelination approach to the treatment of MS.

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Section: Cell Adhesion Moleculesmentioning

confidence: 99%

Promoting remyelination for the treatment of multiple sclerosis: opportunities and challenges

Zhang

Guo

2013

Neurosci. Bull.

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“…L1 is expressed on sprouting primary afferents after dorsal rhizotomy in rats (Runyan et al, 2005) and is implicated as a possible factor for axonal growth following injury to the nervous system (Styren et al, 1995;Aubert et al, 1998;Brook et al, 2000;Roonprapunt et al, 2003;Kubasak et al, 2005;Chen et al, 2007). If L1 is necessary for primary afferent sprouting, we would expect to see little or no sprouting in its absence.…”

Section: L1 Is Not Required For Cgrp-positive Afferent Sproutingmentioning

confidence: 99%

L1 cell adhesion molecule is not required for small-diameter primary afferent sprouting after deafferentation

Runyan

Roy²,

Zhong³

et al. 2007

Neuroscience

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L1 is a cell adhesion molecule associated with axonal outgrowth and fasciculation during spinal cord development and may reiterate its developmental role in adults following injury; L1 is upregulated on certain sprouting and regenerating axons in adults, but it is unclear if L1 expression is necessary for, or contributes to, regrowth of axons. This study asks if L1 is required for small-diameter primary afferents to sprout by conducting unilateral dorsal rhizotomies (6 segments; T10-L2) on both wildtype and L1 mutant mice. First we determined that L1 co-localizes substantially with the peptidergic (calcitonin gene-related peptide; CGRP) but minimally with the nonpeptidergic (isolectin B4; IB4) primary afferents in intact wild-type and L1 mutant mice. However, we encountered a complication using IB4 to identify primary afferents post-rhizotomy; we detected extensive abnormal IB4 expression in the dorsal horn and dorsal columns. Much of this aberrant IB4 labeling is associated with fibrous astrocytes and microglia. Five days after dorsal rhizotomy a large decrease in peptidergic and nonpeptidergic afferents is evident on the deafferented side in both wild-type and L1 mutants. Three months after surgery the peptidergic primary afferents sprouted into the center of the denervated dorsal horn in both wild-type and mutant mice, and quantitative analyses confirmed a sprouting density of similar magnitude in both genotypes. In contrast, we did not detect sprouting in the nonpeptidergic primary afferents in either genotype. These results suggest that the absence of L1 neither diminishes nor enhances sprouting of peptidergic small-diameter primary afferent axons following a dorsal rhizotomy. Keywordscell adhesion molecule; denervated; IB4; CGRP; nociceptors; rhizotomy The cell adhesion molecule L1 (L1 CAM) is an axonal glycoprotein and a member of the immunoglobulin superfamily (Kamiguchi et al., 1997). L1 plays a role in axonal outgrowth, fasciculation, and guidance during spinal cord development (Stallcup et al., 1985;Jessell, 1988;Stoeckli and Landmesser, 1995;Orlino et al., 2000;Tran and Phelps, 2000;Akopians et al., 2003) through homophilic and various heterophilic binding partners such as integrins (αVβ3 and α5β1) and the fibroblast growth factor receptor (Kamiguchi and Lemmon, 1997 Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Lemmon, 1997;Castellani et al., 2000). NIH Public AccessMutations in X-linked L1 in humans cause major developmental errors and result in a group of symptoms that include corpus callosum hypoplasia, spastic paraplegia and hydrocephalus (Fran...

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“…To show that the DRG neuronal adhesion to HEK cells is mediated by DRAGON, we generated a soluble DRAGON-Fc fusion protein similar to those for other molecules involved in adhesion and repulsion such as L1, the ephrins, Robo, and tenascin (Hivert et al, 2002;Rigato et al, 2002;Fuller et al, 2003;Roonprapunt et al, 2003). Purified DRAGON-Fc is detectable by both anti-DRAGON and anti-Fc antibodies (Fig.…”

Section: Dragon and Neuronal Adhesionmentioning

confidence: 99%

DRAGON: A Member of the Repulsive Guidance Molecule-Related Family of Neuronal- and Muscle-Expressed Membrane Proteins Is Regulated by DRG11 and Has Neuronal Adhesive Properties

Samad

Srinivasan²,

Karchewski³

et al. 2004

J. Neurosci.

131

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DRG11, a transcription factor expressed in embryonic dorsal root ganglion (DRG) and dorsal horn neurons, has a role in the development of sensory circuits. We have used a genomic binding strategy to screen for the promoter region of genes regulated by DRG11. One gene with a promoter region binding to the DNA binding domain of DRG11 encodes a novel membrane-associated [glycosylphosphatidylinositol (GPI)-anchored] protein that we call DRAGON. DRAGON expression is transcriptionally regulated by DRG11, and it is coexpressed with DRG11 in embryonic DRG and spinal cord. DRAGON expression in these areas is reduced in DRG11 null mutants. DRAGON is expressed, however, in the neural tube before DRG11, and unlike DRG11 it is expressed in the brain and therefore must be regulated by other transcriptional regulatory elements. DRAGON shares high sequence homology with two other GPI-anchored membrane proteins: the mouse ortholog of chick repulsive guidance molecule (mRGM), which is expressed in the mouse nervous system in areas complementary to DRAGON, and DRAGON-like muscle (DL-M), the expression of which is restricted to skeletal and cardiac muscle. A comparative genomic analysis indicates that the family of RGM-related genes-mRGM, DRAGON, and DL-M-are highly conserved among mammals, zebrafish, chick, and Caenorhabditis elegans but not Drosophila. DRAGON, RGM, and DL-M mRNA expression in the zebrafish embryo is similar to that in the mouse. Neuronal cell adhesion assays indicate that DRAGON promotes and mRGM reduces adhesion of mouse DRG neurons. We show that DRAGON interacts with itself homophilically. The dynamic expression, ordered spatial localization, and adhesive properties of the RGM-related family of membrane-associated proteins are compatible with specific roles in development.

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Soluble Cell Adhesion Molecule L1-Fc Promotes Locomotor Recovery in Rats after Spinal Cord Injury

Cited by 100 publications

References 61 publications

Promoting remyelination for the treatment of multiple sclerosis: opportunities and challenges

Promoting remyelination for the treatment of multiple sclerosis: opportunities and challenges

L1 cell adhesion molecule is not required for small-diameter primary afferent sprouting after deafferentation

DRAGON: A Member of the Repulsive Guidance Molecule-Related Family of Neuronal- and Muscle-Expressed Membrane Proteins Is Regulated by DRG11 and Has Neuronal Adhesive Properties

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