The repair Schwann cell and its function in regenerating nerves

The Journal of Physiology, Journal Year: 2016, Volume and Issue: 594(13), P. 3521 - 3531

Published: Feb. 10, 2016

Abstract Nerve injury triggers the conversion of myelin and non‐myelin (Remak) Schwann cells to a cell phenotype specialized promote repair. Distal damage, these repair provide necessary signals spatial cues for survival injured neurons, axonal regeneration target reinnervation. The involves de‐differentiation together with alternative differentiation, or activation, combination that is typical type conversions often referred as (direct lineage) reprogramming. Thus, injury‐induced reprogramming down‐regulation genes combined activation set repair‐supportive features, including up‐regulation trophic factors, elevation cytokines part innate immune response, clearance by autophagy in macrophage recruitment, formation tracks, Bungner's bands, directing axons their targets. This programme controlled transcriptionally mechanisms involving transcription factor c‐Jun, which rapidly up‐regulated after injury. In absence damage results dysfunctional cell, neuronal death failure functional recovery. although not required development, therefore central future, signalling specifies this requires further analysis so pharmacological tools boost maintain can be developed. image

Language: Английский

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Building the Neuronal Microtubule Cytoskeleton

Neuron, Journal Year: 2015, Volume and Issue: 87(3), P. 492 - 506

Published: Aug. 1, 2015

Language: Английский

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Intrinsic Control of Axon Regeneration

Neuron, Journal Year: 2016, Volume and Issue: 90(3), P. 437 - 451

Published: May 1, 2016

Language: Английский

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Moving beyond the glial scar for spinal cord repair

Nature Communications, Journal Year: 2019, Volume and Issue: 10(1)

Published: Aug. 28, 2019

Abstract Traumatic spinal cord injury results in severe and irreversible loss of function. The triggers a complex cascade inflammatory pathological processes, culminating formation scar. While traditionally referred to as glial scar, the scar fact comprises multiple cellular extracellular components. This multidimensional nature should be considered when aiming understand role scarring limiting tissue repair recovery. In this Review we discuss recent advances understanding composition phenotypic characteristics oversimplification defining binary terms good or bad, development therapeutic approaches target components enable improved functional outcome after injury.

Language: Английский

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Intrinsic mechanisms of neuronal axon regeneration

Nature reviews. Neuroscience, Journal Year: 2018, Volume and Issue: 19(6), P. 323 - 337

Published: April 17, 2018

Language: Английский

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Cell biology of spinal cord injury and repair

Journal of Clinical Investigation, Journal Year: 2017, Volume and Issue: 127(9), P. 3259 - 3270

Published: July 23, 2017

Spinal cord injury (SCI) lesions present diverse challenges for repair strategies. Anatomically complete injuries require restoration of neural connectivity across lesions. incomplete may benefit from augmentation spontaneous circuit reorganization. Here, we review SCI cell biology, which varies considerably three different lesion-related tissue compartments: (a) non-neural lesion core, (b) astrocyte scar border, and (c) surrounding spared but reactive tissue. After SCI, axon growth reorganization are determined by neuron-cell-autonomous mechanisms interactions among neurons, glia, immune other cells. These shaped both the presence absence growth-modulating molecules, vary markedly in compartments. The emerging understanding how biology differs compartments is fundamental to developing rationally targeted

Language: Английский

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Required growth facilitators propel axon regeneration across complete spinal cord injury

Nature, Journal Year: 2018, Volume and Issue: 561(7723), P. 396 - 400

Published: Aug. 28, 2018

Language: Английский

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Systemic administration of epothilone B promotes axon regeneration after spinal cord injury

Science, Journal Year: 2015, Volume and Issue: 348(6232), P. 347 - 352

Published: March 13, 2015

After central nervous system (CNS) injury, inhibitory factors in the lesion scar and poor axon growth potential prevent regeneration. Microtubule stabilization reduces scarring promotes growth. However, cellular mechanisms of this dual effect remain unclear. Here, delayed systemic administration a blood-brain barrier-permeable microtubule-stabilizing drug, epothilone B (epoB), decreased after rodent spinal cord injury (SCI) by abrogating polarization directed migration scar-forming fibroblasts. Conversely, reactivated neuronal inducing concerted microtubule polymerization into tip, which propelled through an environment. Together, these drug-elicited effects promoted regeneration improved motor function SCI. With recent clinical approval, epothilones hold promise for use CNS injury.

Language: Английский

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DLK initiates a transcriptional program that couples apoptotic and regenerative responses to axonal injury

Proceedings of the National Academy of Sciences, Journal Year: 2013, Volume and Issue: 110(10), P. 4039 - 4044

Published: Feb. 19, 2013

The cell intrinsic factors that determine whether a neuron regenerates or undergoes apoptosis in response to axonal injury are not well defined. Here we show the mixed-lineage dual leucine zipper kinase (DLK) is an essential upstream mediator of both these divergent outcomes same type. Optic nerve crush leads rapid elevation DLK protein, first axons retinal ganglion cells (RGCs) and then their bodies. required for majority gene expression changes RGCs initiated by injury, including induction proapoptotic regeneration-associated genes. Deletion retina results robust sustained protection from degeneration after optic injury. Despite this improved survival, number regrow beyond site substantially reduced, even when tumor suppressor phosphatase tensin homolog (PTEN) deleted enhance growth potential. These findings demonstrate seemingly contradictory responses mechanistically coupled through DLK-based damage detection mechanism.

Language: Английский

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Dual Leucine Zipper Kinase Is Required for Retrograde Injury Signaling and Axonal Regeneration

Neuron, Journal Year: 2012, Volume and Issue: 74(6), P. 1015 - 1022

Published: June 1, 2012

Language: Английский

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