The Role of Axon Transport in Neuroprotection and Regeneration

Overview

Journal Dev Neurobiol

Specialties Biology
Neurology

Date 2018 Jul 21

PMID 30027690

Citations 10

Authors

Sahil H Shah

Jeffrey L Goldberg

Affiliations

Soon will be listed here.

Abstract

Retinal ganglion cells and other central nervous system neurons fail to regenerate after injury. Understanding the obstacles to survival and regeneration, and overcoming them, is key to preserving and restoring function. While comparisons in the cellular changes seen in these non-regenerative cells with those that do have intrinsic regenerative ability has yielded many candidate genes for regenerative therapies, complete visual recovery has not yet been achieved. Insights gained from neurodegenerative diseases, like glaucoma, underscore the importance of axonal transport of organelles, mRNA, and effector proteins in injury and disease. Targeting molecular motor networks, and their cargoes, may be necessary for realizing complete axonal regeneration and vision restoration.

Citing Articles

Optineurin-facilitated axonal mitochondria delivery promotes neuroprotection and axon regeneration.

Liu D, Webber H, Bian F, Xu Y, Prakash M, Feng X Nat Commun. 2025; 16(1):1789.

PMID: 39979261 PMC: 11842812. DOI: 10.1038/s41467-025-57135-8.

KIF5A regulates axonal repair and time-dependent axonal transport of SFPQ granules and mitochondria in human motor neurons.

Guerra San Juan I, Brunner J, Eggan K, Toonen R, Verhage M bioRxiv. 2024; .

PMID: 39314491 PMC: 11418931. DOI: 10.1101/2024.09.06.611684.

The IL-33/ST2 Axis Protects Retinal Ganglion Cells by Modulating the Astrocyte Response After Optic Nerve Injury.

Qian Z, Jiao M, Zhang N, Tang X, Liu S, Zhang F Neurosci Bull. 2024; 41(1):61-76.

PMID: 39190095 PMC: 11748692. DOI: 10.1007/s12264-024-01279-y.

Optineurin-facilitated axonal mitochondria delivery promotes neuroprotection and axon regeneration.

Liu D, Webber H, Bian F, Xu Y, Prakash M, Feng X bioRxiv. 2024; .

PMID: 38617277 PMC: 11014509. DOI: 10.1101/2024.04.02.587832.

Genes in Axonal Regeneration.

Wu W, Zhang J, Chen Y, Chen Q, Liu Q, Zhang F Mol Neurobiol. 2024; 61(10):7431-7447.

PMID: 38388774 DOI: 10.1007/s12035-024-04049-z.

References

Saha A, Hill J, Utton M, Asuni A, Ackerley S, Grierson A . Parkinson's disease alpha-synuclein mutations exhibit defective axonal transport in cultured neurons. J Cell Sci. 2004; 117(Pt 7):1017-24. DOI: 10.1242/jcs.00967. View

Fischer D, He Z, Benowitz L . Counteracting the Nogo receptor enhances optic nerve regeneration if retinal ganglion cells are in an active growth state. J Neurosci. 2004; 24(7):1646-51. PMC: 6730473. DOI: 10.1523/JNEUROSCI.5119-03.2004. View

Smith R, Lerch-Haner J, Pardinas J, Buchser W, Bixby J, Lemmon V . Transcriptional profiling of intrinsic PNS factors in the postnatal mouse. Mol Cell Neurosci. 2010; 46(1):32-44. PMC: 3003944. DOI: 10.1016/j.mcn.2010.07.015. View

Toda H, Mochizuki H, Flores 3rd R, Josowitz R, Krasieva T, Lamorte V . UNC-51/ATG1 kinase regulates axonal transport by mediating motor-cargo assembly. Genes Dev. 2008; 22(23):3292-307. PMC: 2600757. DOI: 10.1101/gad.1734608. View

McKerracher L, Vidal-Sanz M, Essagian C, Aguayo A . Selective impairment of slow axonal transport after optic nerve injury in adult rats. J Neurosci. 1990; 10(8):2834-41. PMC: 6570264. View

Watkins T, Wang B, Huntwork-Rodriguez S, Yang J, Jiang Z, Eastham-Anderson J . DLK initiates a transcriptional program that couples apoptotic and regenerative responses to axonal injury. Proc Natl Acad Sci U S A. 2013; 110(10):4039-44. PMC: 3593899. DOI: 10.1073/pnas.1211074110. View

Santina L, Inman D, Lupien C, Horner P, Wong R . Differential progression of structural and functional alterations in distinct retinal ganglion cell types in a mouse model of glaucoma. J Neurosci. 2013; 33(44):17444-57. PMC: 3812509. DOI: 10.1523/JNEUROSCI.5461-12.2013. View

Yan D, Wu Z, Chisholm A, Jin Y . The DLK-1 kinase promotes mRNA stability and local translation in C. elegans synapses and axon regeneration. Cell. 2009; 138(5):1005-18. PMC: 2772821. DOI: 10.1016/j.cell.2009.06.023. View

Qin S, Zou Y, Zhang C . Cross-talk between KLF4 and STAT3 regulates axon regeneration. Nat Commun. 2013; 4:2633. PMC: 3867821. DOI: 10.1038/ncomms3633. View

10.

Blackmore M, Wang Z, Lerch J, Motti D, Zhang Y, Shields C . Krüppel-like Factor 7 engineered for transcriptional activation promotes axon regeneration in the adult corticospinal tract. Proc Natl Acad Sci U S A. 2012; 109(19):7517-22. PMC: 3358880. DOI: 10.1073/pnas.1120684109. View

11.

Park K, Liu K, Hu Y, Kanter J, He Z . PTEN/mTOR and axon regeneration. Exp Neurol. 2010; 223(1):45-50. DOI: 10.1016/j.expneurol.2009.12.032. View

12.

Yorifuji H, Inagaki M, Hirokawa N . The phosphorylation of kinesin regulates its binding to synaptic vesicles. J Biol Chem. 1992; 267(33):23930-6. View

13.

Stokin G, Lillo C, Falzone T, Brusch R, Rockenstein E, Mount S . Axonopathy and transport deficits early in the pathogenesis of Alzheimer's disease. Science. 2005; 307(5713):1282-8. DOI: 10.1126/science.1105681. View

14.

Welsbie D, Mitchell K, Jaskula-Ranga V, Sluch V, Yang Z, Kim J . Enhanced Functional Genomic Screening Identifies Novel Mediators of Dual Leucine Zipper Kinase-Dependent Injury Signaling in Neurons. Neuron. 2017; 94(6):1142-1154.e6. PMC: 5553555. DOI: 10.1016/j.neuron.2017.06.008. View

15.

Loh K, Stawski P, Draycott A, Udeshi N, Lehrman E, Wilton D . Proteomic Analysis of Unbounded Cellular Compartments: Synaptic Clefts. Cell. 2016; 166(5):1295-1307.e21. PMC: 5167540. DOI: 10.1016/j.cell.2016.07.041. View

16.

Hirokawa N . Kinesin and dynein superfamily proteins and the mechanism of organelle transport. Science. 1998; 279(5350):519-26. DOI: 10.1126/science.279.5350.519. View

17.

Chevalier-Larsen E, Holzbaur E . Axonal transport and neurodegenerative disease. Biochim Biophys Acta. 2006; 1762(11-12):1094-108. DOI: 10.1016/j.bbadis.2006.04.002. View

18.

MacAskill A, Rinholm J, Twelvetrees A, Arancibia-Carcamo I, Muir J, Fransson A . Miro1 is a calcium sensor for glutamate receptor-dependent localization of mitochondria at synapses. Neuron. 2009; 61(4):541-55. PMC: 2670979. DOI: 10.1016/j.neuron.2009.01.030. View

19.

Yanik M, Cinar H, Cinar H, Chisholm A, Jin Y, Ben-Yakar A . Neurosurgery: functional regeneration after laser axotomy. Nature. 2004; 432(7019):822. DOI: 10.1038/432822a. View

20.

Chen M, Huber A, van der Haar M, Frank M, Schnell L, Spillmann A . Nogo-A is a myelin-associated neurite outgrowth inhibitor and an antigen for monoclonal antibody IN-1. Nature. 2000; 403(6768):434-9. DOI: 10.1038/35000219. View