Neuronal Intrinsic Regenerative Capacity: The Impact of Microtubule Organization and Axonal Transport

Abstract

In the adult vertebrate central nervous system, axons generally fail to regenerate. In contrast, peripheral nervous system axons are able to form a growth cone and regenerate upon lesion. Among the multiple intrinsic mechanisms leading to the formation of a new growth cone and to successful axon regrowth, cytoskeleton organization and dynamics is central. Here we discuss how multiple pathways that define the regenerative capacity converge into the regulation of the axonal microtubule cytoskeleton and transport. We further explore the use of dorsal root ganglion neurons as a model to study the neuronal regenerative ability. Finally, we address some of the unanswered questions in the field, including the mechanisms by which axonal transport might be modulated by injury, and the relationship between microtubule organization, dynamics, and axonal transport. © 2018 Wiley Periodicals, Inc. Develop Neurobiol 00: 000-000, 2018.

HDAC6 regulates microtubule stability and clustering of AChRs at neuromuscular junctions

“…In neurons, the MT network is known to participate in neuronal polarization, axonal transport, axonal growth, and regeneration (Murillo and Mendes Sousa, 2018;Janke and Kneussel, 2010). Accordingly, inhibition of HDAC6 in cortical and dorsal root ganglion neurons enhances tubulin acetylation and promotes axon growth, thereby demonstrating the need for stable MTs within axons for cargo delivery (Rivieccio et al, 2009).…”

Vitamin B12 Enhances Nerve Repair and Improves Functional Recovery After Traumatic Brain Injury by Inhibiting ER Stress-Induced Neuron Injury

“…Microtubules stability is a major determinant of axonal growth and neuronal polarization during axon formation (Murillo and Sousa, 2018). A previous study had demonstrated that the administration of fibroblast growth factor 13 (FGF13) maintained microtubule stability, and promoted axon formation and neuronal polarization after spinal cord injury (Li et al, 2018).…”

Microtubule dynamics in healthy and injured neurons

“…While the relationship between increased microtubule dynamics/ reduced microtubule stability and neurite pruning and degeneration is quite intuitive, more complex changes in stability are associated with axon regeneration. First, there are local microtubule changes at the injury site that are important for setting the stage for regeneration (Blanquie & Bradke, 2018;Murillo & Mendes, 2018). In a fun study on Aplysia axons, severing was shown to cause changes in microtubule polarity just proximal to the injury site.…”