Myelin-associated inhibitors of axonal regeneration in the adult mammalian CNS

Filbin, Marie T.

doi:10.1038/nrn1195

Cited by 775 publications

(550 citation statements)

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“…Axonal regeneration following adult CNS injury is prevented by multiple factors, including the presence of inhibitory proteins that actively block axon regrowth (Filbin, 2003;Laabs et al, 2005;Schwab, 2004;Silver and Miller, 2004). The development of therapies to promote axonal regeneration will require overcoming these disparate inhibitory influences.…”

Section: Discussionmentioning

confidence: 99%

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MICAL flavoprotein monooxygenases: Expression during neural development and following spinal cord injuries in the rat

Pasterkamp

Dai

Terman³

et al. 2006

Molecular and Cellular Neuroscience

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Section: Discussionmentioning

confidence: 99%

“…CNS myelin and chondroitin sulfate proteoglycans (CSPGs) are potent inhibitors of regenerative axon growth (Filbin, 2003;Laabs et al, 2005;Schwab, 2004;Silver and Miller, 2004). Therefore, we tested whether the inhibitory effects of CNS myelin or CSPGs could be blocked by EGCG.…”

Section: The Flavonoid Egcg Attenuates Axon Repulsion Induced By Sema3smentioning

confidence: 99%

MICAL flavoprotein monooxygenases: Expression during neural development and following spinal cord injuries in the rat

Pasterkamp

Dai

Terman³

et al. 2006

Molecular and Cellular Neuroscience

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“…These extrinsic factors include the absence of a growth-promoting substrate, inflammation following SCI, reactive astrogliosis, inhibitory extracellular matrix proteins, myelin inhibitory proteins, induction of repulsive guidance cues, and the lack of trophic support in the injured CNS [27][28][29][30][31][32][33]. There are numerous experimental strategies for targeting these extrinsic mechanisms, which include providing growth-promoting substrates, mediating the inflammatory response to SCI, eliminating reactive astrogliosis, reducing inhibitory extracellular matrix and myelin proteins, attenuating repulsive guidance signals, as well as providing growth-promoting neurotrophic signals.…”

Section: Mechanisms Underlying the Failure Of Cns Regenerationmentioning

confidence: 99%

Neurotrophins: Potential Therapeutic Tools for the Treatment of Spinal Cord Injury

Hollis

Tuszynski

2011

Neurotherapeutics

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Spinal cord injury permanently disrupts neuroanatomical circuitry and can result in severe functional deficits. These functional deficits, however, are not immutable and spontaneous recovery occurs in some patients. It is highly likely that this recovery is dependent upon spared tissue and the endogenous plasticity of the central nervous system. Neurotrophic factors are mediators of neuronal plasticity throughout development and into adulthood, affecting proliferation of neuronal precursors, neuronal survival, axonal growth, dendritic arborization and synapse formation. Neurotrophic factors are therefore excellent candidates for enhancing axonal plasticity and regeneration after spinal cord injury. Understanding growth factor effects on axonal growth and utilizing them to alter the intrinsic limitations on regenerative growth will provide potent tools for the development of translational therapeutic interventions for spinal cord injury.Keywords Neurotrophin . spinal cord injury . regeneration . axon plasticity . functional recovery Human Spinal Cord InjuryTraumatic injury of the spinal cord can produce a range of debilitating effects and permanently alter the capabilities and quality of life of its surviving victims. Damage to the central nervous system (CNS) in general results in destruction of neuronal circuitry. Contusion, compression, and penetration injuries of the spinal cord can interrupt the flow of sensory and motor information between the brain and periphery [1]. Depending on the location and severity of the injury, deficits can range from weakness of limb movement to total paralysis and ventilator-assisted respiration. Spontaneous functional recovery is limited, but can and often does occur in patients with initial sparing of sensorimotor function [2]. This recovery, which plateaus between 12 to 18 months, is very likely due to sparing and sprouting of axons within the zone of partial preservation, an area where some motor function remains intact, immediately adjacent to the lesion site [2].Approximately 40% of humans that sustain spinal cord injury (SCI) exhibit improvement from their early postinjury baseline, and this spontaneous recovery can range from modest to extensive [2]. Spontaneous recovery primarily appears to depend on the extent of tissue sparing at the injury site, allowing compensatory axonal sprouting and systems reorganization at levels ranging from the spinal cord to the cerebral cortex [3][4][5][6][7][8][9][10]. However, in cases of more severe injuries, means of enhancing endogenous levels of axonal sprouting and inducing true axonal regeneration are required to enhance functional outcomes.Electronic supplementary material The online version of this article

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“…In contrast, MAG binding to an NgR1 homolog, NgR2, is sialic acid-dependent, and NgR2 can also mediate the inhibitory effect of MAG in vitro (Venkatesh et al, 2005). MAG has been extensively used to mimic the effect of CNS myelin on neurite growth (Filbin, 2003). However, there has been a lack of evidence demonstrating MAG's role as an inhibitor of CNS axon regeneration based on in vivo studies either using MAG mutant mice (Bartsch et al, 1995) or function blocking agents.…”

Section: Magmentioning

confidence: 99%

White matter inhibitors in CNS axon regeneration failure

Xie

Zheng

2008

Experimental Neurology

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Multiple lines of evidence have indicated that the inability of adult mammalian central nervous system (CNS) axons to regenerate after injury is partly due to the growth inhibitory property of central myelin. Three prototypical myelin-associated inhibitors of neurite outgrowth have been identified, including Nogo, myelin-associated glycoprotein (MAG), oligodendrocyte-myelin glycoprotein (OMgp). These inhibitory ligands, their receptors and signaling pathways are being intensively investigated for their roles in CNS axon regeneration failure. In addition, several members of the axon guidance molecules have been implicated in restricting CNS axon regeneration, some of which are expressed by mature oligodendrocytes. Here we review in vitro and in vivo studies of these molecules in neurite growth and in axon regeneration failure and discuss the implications of these studies. While the increasing number of potential axon regeneration inhibitors highlights the complexity of the restrictive CNS environment, it provides new windows of opportunity as well as new challenges for therapeutic development for spinal cord injury and related neurological conditions.

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Myelin-associated inhibitors of axonal regeneration in the adult mammalian CNS

Cited by 775 publications

References 105 publications

MICAL flavoprotein monooxygenases: Expression during neural development and following spinal cord injuries in the rat

MICAL flavoprotein monooxygenases: Expression during neural development and following spinal cord injuries in the rat

Neurotrophins: Potential Therapeutic Tools for the Treatment of Spinal Cord Injury

White matter inhibitors in CNS axon regeneration failure

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