Axon Regeneration in the Central Nervous System: Facing the Challenges from the Inside

Annual Review of Cell and Developmental Biology, Journal Year: 2018, Volume and Issue: 34(1), P. 495 - 521

Published: July 25, 2018

After an injury in the adult mammalian central nervous system (CNS), lesioned axons fail to regenerate. This failure regenerate contrasts with axons' remarkable potential grow during embryonic development and after peripheral (PNS). Several intracellular mechanisms-including cytoskeletal dynamics, axonal transport trafficking, signaling transcription of regenerative programs, epigenetic modifications-control axon regeneration. In this review, we describe how manipulation intrinsic mechanisms elicits a response different organisms strategies are implemented form basis future treatment CNS injury.

Language: Английский

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The Role of the Microtubule Cytoskeleton in Neurodevelopmental Disorders

Frontiers in Cellular Neuroscience, Journal Year: 2018, Volume and Issue: 12

Published: June 14, 2018

Neurons depend on the highly dynamic microtubule (MT) cytoskeleton for many different processes during early embryonic development including cell division and migration, intracellular trafficking signal transduction, as well proper axon guidance synapse formation. The coordination support from MTs is crucial newly formed neurons to migrate appropriately in order establish neural connections. Once connections are made, provide structural integrity maintain connectivity throughout development. Abnormalities migration due genetic mutations of MT-associated proteins can lead detrimental developmental defects. Growing evidence suggests that these associated with neurodevelopmental disorders, intellectual disabilities (ID) autism spectrum disorders (ASD). In this review article, we highlight role MT context neurodevelopment summarize various related may underlie or contribute disorders.

Language: Английский

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α-Tubulin Tyrosination and CLIP-170 Phosphorylation Regulate the Initiation of Dynein-Driven Transport in Neurons

Cell Reports, Journal Year: 2016, Volume and Issue: 14(11), P. 2637 - 2652

Published: March 1, 2016

Motor-cargo recruitment to microtubules is often the rate-limiting step of intracellular transport, and defects in this can cause neurodegenerative disease. Here, we use vitro reconstitution assays with single-molecule resolution, live-cell transport primary neurons, computational image analysis, computer simulations investigate factors regulating retrograde initiation distal axon. We find that phosphorylation cytoskeletal-organelle linker protein CLIP-170 post-translational modifications microtubule track combine precisely control transport. Computer organelle dynamics axon indicate while primarily regulates time encounter, tyrosination state lattice likelihood binding. These mechanisms interact a manner sensitive specialized cytoskeletal architecture neuron.

Language: Английский

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Growth factors-based therapeutic strategies and their underlying signaling mechanisms for peripheral nerve regeneration

Acta Pharmacologica Sinica, Journal Year: 2020, Volume and Issue: 41(10), P. 1289 - 1300

Published: March 2, 2020

Abstract Peripheral nerve injury (PNI), one of the most common concerns following trauma, can result in a significant loss sensory or motor function. Restoration injured nerves requires complex cellular and molecular response to rebuild functional axons so that they accurately connect with their original targets. However, there is no optimized therapy for complete recovery after PNI. Supplementation exogenous growth factors (GFs) an emerging versatile therapeutic strategy promoting regeneration recovery. GFs activate downstream targets various signaling cascades through binding corresponding receptors exert multiple effects on neurorestoration tissue regeneration. simple administration insufficient reconstructing PNI due short half‑life rapid deactivation body fluids. To overcome these shortcomings, several conduits derived from biological synthetic materials have been developed. Their good biocompatibility biofunctionality made them suitable vehicle delivery support peripheral After repairing defects, controlled release conduit structures able continuously improve axonal outcome. Thus, therapies factor (GF) systems received increasing attention recent years. Here, we mainly review capacity incorporation into guides In addition, possible mechanisms GF family exerting are also emphasized.

Language: Английский

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DendritesIn VitroandIn VivoContain Microtubules of Opposite Polarity and Axon Formation Correlates with Uniform Plus-End-Out Microtubule Orientation

Journal of Neuroscience, Journal Year: 2016, Volume and Issue: 36(4), P. 1071 - 1085

Published: Jan. 27, 2016

In cultured vertebrate neurons, axons have a uniform arrangement of microtubules with plus-ends distal to the cell body (plus-end-out), whereas dendrites contain mixed polarity orientations both plus-end-out and minus-end-out oriented microtubules. Rather than non-uniform microtubules, uniparallel are signature in Drosophila Caenorhabditis elegans neurons. To determine whether microtubule organization is conserved feature dendrites, we used live-cell imaging systematically analyze plus-end primary cultures rat hippocampal cortical dentate granule cells mouse organotypic slices, layer 2/3 pyramidal neurons somatosensory cortex living mice. vitro vivo , all had orientation axons, orientations. When dendritic were severed by laser-based microsurgery, detected equal numbers plus- throughout processes. generally more stable comparable axons. Interestingly, at early stages neuronal development nonpolarized cells, newly formed neurites already contained opposite polarity, suggesting that establishment occurs during axon formation. We propose model which selective formation critical process underlying polarization. SIGNIFICANCE STATEMENT Live-cell was neuron specific only Based on these findings, authors

Language: Английский

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