Transgenic overexpression of the cell adhesion molecule L1 in neurons facilitates recovery after mouse spinal cord injury

Jakovčevski, Igor; Djogo, Nevena; Hölters, L.S.; Szpotowicz, Emanuela; Schachner, Melitta

doi:10.1016/j.neuroscience.2013.07.067

Cited by 25 publications

(21 citation statements)

References 42 publications

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“…Previous research into the inhibition of glial scar formation mainly focused either on suppressing glial cell proliferation [15] or on decreasing the secretion of ECM [16] and rarely combined the mentioned two aspects to achieve regulation. Therefore, we wished to identify an effective method that can reduce the expression of both intracellular and extracellular components to simultaneously suppress physical and chemical barriers, thus providing more effective inhibition of glial scar formation.…”

Section: Introductionmentioning

confidence: 99%

Curcumin improves neural function after spinal cord injury by the joint inhibition of the intracellular and extracellular components of glial scar

Yuan

Zou

Xiang

et al. 2015

Journal of Surgical Research

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Section: Introductionmentioning

confidence: 99%

Curcumin improves neural function after spinal cord injury by the joint inhibition of the intracellular and extracellular components of glial scar

Yuan

Zou

Xiang

et al. 2015

Journal of Surgical Research

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“…The beneficial effects of L1 on long-term functional recovery after SCI have been well demonstrated ( Jakovcevski et al, 2013 ; Kataria et al, 2016 ; Roonprapunt et al, 2003 ). L1 expression is upregulated and promotes regenerative axon regrowth/sprouting and improves behavioral outcomes after CNS injury ( Schäfer and Frotscher, 2012 ).…”

Section: Discussionmentioning

confidence: 98%

“…The neural cell adhesion molecule L1 (L1CAM) has been shown to enhance regeneration in the injured spinal cord and poses a promising therapeutic target ( Chen et al, 2016 ; Jakovcevski et al, 2013 ; Loers et al, 2014a ; Lutz et al, 2016 ; Yoo et al, 2014 ). L1 is a member of the immunoglobulin superfamily ( Rathjen et al, 1987 ) and contains six immunoglobulin-like domains and five fibronectin type III domains, followed by a transmembrane domain and a short cytoplasmic domain.…”

Section: Introductionmentioning

confidence: 99%

The small molecule mimetic agonist trimebutine of adhesion molecule L1 contributes to functional recovery after spinal cord injury in mice

Jiang

et al. 2017

Disease Models &Amp; Mechanisms

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Curing spinal cord injury (SCI) in mammals is a daunting task because of the lack of permissive mechanisms and strong inhibitory responses at and around the lesion. The neural cell adhesion molecule L1CAM (L1) has been shown to favor axonal regrowth and enhance neuronal survival and synaptic plasticity but delivery of full-length L1 or its extracellular domain could encounter difficulties in translation to therapy in humans. We have, therefore, identified several small organic compounds that bind to L1 and stimulate neuronal survival, neuronal migration and neurite outgrowth in an L1-dependent manner. Here, we assessed the functions of two L1 mimetics, trimebutine and honokiol, in regeneration following SCI in young adult mice. Using the Basso Mouse Scale (BMS) score, we found that ground locomotion in trimebutine-treated mice recovered better than honokiol-treated or vehicle-receiving mice. Enhanced hindlimb locomotor functions in the trimebutine group were observed at 6 weeks after SCI. Immunohistology of the spinal cords rostral and caudal to the lesion site showed reduced areas and intensities of glial fibrillary acidic protein immunoreactivity in both trimebutine and honokiol groups, whereas increased regrowth of axons was observed only in the trimebutine-treated group. Both L1- and L1 mimetic-mediated intracellular signaling cascades in the spinal cord lesion sites were activated by trimebutine and honokiol, with trimebutine being more effective than honokiol. These observations suggest that trimebutine and, to a lesser extent under the present experimental conditions, honokiol have a potential for therapy in regeneration of mammalian spinal cord injuries.

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“…Knowledge of the presence of other adhesion molecules on mature CNS axons is limited. Type 1 and 2 cadherins and neurexins are present in synapses, so they may well be present on axon shafts, and other adhesion molecules such as L1 and NCAM are present during development, but L1 protein is not detectable in the corticospinal tract of adult mice, even when overexpressed [67]. Growth factor receptors are drivers of axon signalling which can promote growth, but here again some key receptors are excluded from corticospinal axons.…”

Section: The Axonal Surfacementioning

confidence: 99%

The Struggle to Make CNS Axons Regenerate: Why Has It Been so Difficult?

Fawcett

2019

Neurochem Res

100

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Axon regeneration in the CNS is inhibited by many extrinsic and intrinsic factors. Because these act in parallel, no single intervention has been sufficient to enable full regeneration of damaged axons in the adult mammalian CNS. In the external environment, NogoA and CSPGs are strongly inhibitory to the regeneration of adult axons. CNS neurons lose intrinsic regenerative ability as they mature: embryonic but not mature neurons can grow axons for long distances when transplanted into the adult CNS, and regeneration fails with maturity in in vitro axotomy models. The causes of this loss of regeneration include partitioning of neurons into axonal and dendritic fields with many growth-related molecules directed specifically to dendrites and excluded from axons, changes in axonal signalling due to changes in expression and localization of receptors and their ligands, changes in local translation of proteins in axons, and changes in cytoskeletal dynamics after injury. Also with neuronal maturation come epigenetic changes in neurons, with many of the transcription factor binding sites that drive axon growth-related genes becoming inaccessible. The overall aim for successful regeneration is to ensure that the right molecules are expressed after axotomy and to arrange for them to be transported to the right place in the neuron, including the damaged axon tip.

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Transgenic overexpression of the cell adhesion molecule L1 in neurons facilitates recovery after mouse spinal cord injury

Cited by 25 publications

References 42 publications

Curcumin improves neural function after spinal cord injury by the joint inhibition of the intracellular and extracellular components of glial scar

Curcumin improves neural function after spinal cord injury by the joint inhibition of the intracellular and extracellular components of glial scar

The small molecule mimetic agonist trimebutine of adhesion molecule L1 contributes to functional recovery after spinal cord injury in mice

The Struggle to Make CNS Axons Regenerate: Why Has It Been so Difficult?

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