Glial inhibition of CNS axon regeneration

Yiu, Glenn; He, Zhigang

doi:10.1038/nrn1956

Cited by 1,314 publications

(1,159 citation statements)

References 126 publications

(7 reference statements)

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“…Myelin and myelin debris contain several myelin-associated molecules that inhibit regeneration [33][34][35] , among which the Nogo-A N-terminal region (amino-Nogo-A) is one of the most potent inhibitors. inhibition of Nogo-A increases axon plasticity and regeneration and improves functional recovery [36][37][38] .…”

Section: Chabc and Blocking Myelin Inhibitorsmentioning

confidence: 99%

Combination treatment with chondroitinase ABC in spinal cord injury—breaking the barrier

Zhao

Fawcett

2013

Neurosci. Bull.

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After spinal cord injury (SCi), re-establishing functional circuitry in the damaged central nervous system (CNS) faces multiple challenges including lost tissue volume, insufficient intrinsic growth capacity of adult neurons, and the inhibitory environment in the damaged CNS. Several treatment strategies have been developed over the past three decades, but successful restoration of sensory and motor functions will probably require a combination of approaches to address different aspects of the problem. Degradation of the chondroitin sulfate proteoglycans with the chondroitinase ABC (ChABC) enzyme removes a regeneration barrier from the glial scar and increases plasticity in the CNS by removing perineuronal nets. its mechanism of action does not clash or overlap with most of the other treatment strategies, making ChABC an attractive candidate as a combinational partner with other methods. in this article, we review studies in rat SCi models using ChABC combined with other treatments including cell implantation, growth factors, myelin-inhibitory molecule blockers, and ion channel expression. We discuss possible ways to optimize treatment protocols for future combinational studies. To date, combinational therapies with ChABC have shown synergistic effects with several other strategies in enhancing functional recovery after SCi. These combinatorial approaches can now be developed for clinical application.

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Section: Chabc and Blocking Myelin Inhibitorsmentioning

confidence: 99%

Combination treatment with chondroitinase ABC in spinal cord injury—breaking the barrier

Zhao

Fawcett

2013

Neurosci. Bull.

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“…Inhibitory molecules in the environment of the adult central nervous system, such as the myelin-associated inhibitors and proteoglycans in glial scars, were thought to be the major cause of the lack of regeneration for many years [1] .…”

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confidence: 99%

An update on spinal cord injury research

Zou

2013

Neurosci. Bull.

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Spinal cord injury (SCI) is an ever-increasing challenge.Severe injury can cause long-term loss of sensory and motor functions, as well as other chronic conditions, such as neuropathic pain and autonomic dysreflexia. So far, most research has been focused on acute injury. However, due to the lack of treatment, more and more individuals with this condition enter a chronic state, to which very little research effort has been dedicated. SCI is a complex condition. It involves damage to axons, death of neurons, neuroinflammation, glial scar formation, loss of myelin, and lack of remyelination. It is clear that effective treatment will require combinatorial approaches. The 12 invited articles for this special issue on SCI provide an update on many of these areas of SCI research. Here, I highlight the articles and reviews by theme.Severe SCI involves severing of axons, breaking ascending and descending connections. Inhibitory molecules in the environment of the adult central nervous system, such as the myelin-associated inhibitors and proteoglycans in glial scars, were thought to be the major cause of the lack of regeneration for many years [1] .However, efforts to regenerate axons across a lesion site in the mammalian spinal cord by overcoming this inhibition have not been successful. In some cases, axon regeneration into cell grafts can be achieved, as in studies using preconditioning lesion paradigms of sensory axons [2] .But few axons project beyond the lesion and reach longrange targets. In recent years, more attention has been shifted to enhancing the intrinsic growth capacity of adult central nervous system axons. Deletion of pTEN (phosphatase and tensin homolog) induces unprecedented regeneration across the fully-transacted spinal cord [3] .Neurons derived from embryos or induced pluripotent stem cells that have strong intrinsic growth properties can ignore inhibitory cues in the adult spinal cord and grow long distances up and down the cord [4] . In partial injury, rerouting and sprouting of axons result in circuit reorganization in the spared tissue and have been shown to be effective in restoring function using a combination of pharmacological and electrophysiological stimulation and robot-assisted rehabilitation techniques [5,6] . Molecular mechanisms that promote or inhibit axon growth have been studied, using various injury paradigms, in different neuronal types and species. Some species have poor central regeneration, whereas others have the capacity to regenerate. Axons in the peripheral nervous system of mammals also show extensive regeneration. The review by Martin Oudega of the University of Pittsburgh [7] provides a comprehensive discussion comparing the molecular mechanisms found in mammals and zebrafish.These comparisons allow for a better understanding of the underlying principles. Remarkably, regeneration in the zebrafish central nervous system is also incomplete. Some axon tracts can regenerate but others cannot. This makes zebrafish an interesting model system for SCI research along with the ...

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“…Identified in adult myelin, these molecules exert strong inhibitory effect on axonal regrowth following injury [11]. Nogo-A regulates axonal plasticity and has a key role in inhibiting axon regrowth in the damaged CNS [12].…”

Section: Signalling Molecules Implicated In Axon Guidancementioning

confidence: 99%

“…Mainly integrins [67] Contact adhesion or repulsion [67] Cell Adhesion Molecules (CAMs) (IgSF-CAMs, Cadherins) Homophilic or heterophilic interactions within class [67] Contact adhesion or repulsion [67] Prototypic myelin inhibitors (Nogo-A, MAG, OMgp) NgR1, NgR2, Lingo1, p75NTR, TNFR, PirB, Integrins [11,12] Inhibitors of axonal growth and regeneration; restriction of axonal plasticity [11,12] …”

Section: Tablesmentioning

confidence: 99%

Roles of innervation in developing and regenerating orofacial tissues

Pagella

Jiménez-Rojo

Mitsiadis

2014

Cell. Mol. Life Sci.

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The head is innervated by 12 cranial nerves (I-XII) that regulate its sensory and motor functions. Cranial nerves are composed of sensory, motor, or mixed neuronal populations. Sensory neurons perceive generally somatic sensations such as pressure, pain, and temperature. These neurons are also involved in smell, vision, taste, and hearing. Motor neurons ensure the motility of all muscles and glands. Innervation plays an essential role in the development of the various orofacial structures during embryogenesis. Hypoplastic cranial nerves often lead to abnormal development of their target organs and tissues. For example, Möbius syndrome is a congenital disease characterized by defective innervation (i.e., abducens (VI) and facial (VII) nerves), deafness, tooth anomalies, and cleft palate. Hence, it is obvious that the peripheral nervous system is needed for both development and function of orofacial structures. Nerves have a limited capacity to regenerate. However, neural stem cells, which could be used as sources for neural tissue maintenance and repair, have been found in adult neuronal tissues. Similarly, various adult stem cell populations have been isolated from almost all organs of the human body. Stem cells are tightly regulated by their microenvironment, the stem cell niche. Deregulation of adult stem cell behavior results in the development of pathologies such as tumor formation or early tissue senescence. It is thus essential to understand the factors that regulate the functions and maintenance of stem cells. Yet, the potential importance of innervation in the regulation of stem cells and/or their niches in most organs and tissues is largely unexplored. This review focuses on the potential role of innervation in the development and homeostasis of orofacial structures and discusses its possible association with stem cell populations during tissue repair.

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Glial inhibition of CNS axon regeneration

Cited by 1,314 publications

References 126 publications

Combination treatment with chondroitinase ABC in spinal cord injury—breaking the barrier

Combination treatment with chondroitinase ABC in spinal cord injury—breaking the barrier

An update on spinal cord injury research

Roles of innervation in developing and regenerating orofacial tissues

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