» Articles » PMID: 37259916

Disruption of Axonal Transport in Neurodegeneration

Overview
Journal J Clin Invest
Specialty General Medicine
Date 2023 Jun 1
PMID 37259916
Authors
Affiliations
Soon will be listed here.
Abstract

Neurons are markedly compartmentalized, which makes them reliant on axonal transport to maintain their health. Axonal transport is important for anterograde delivery of newly synthesized macromolecules and organelles from the cell body to the synapse and for the retrograde delivery of signaling endosomes and autophagosomes for degradation. Dysregulation of axonal transport occurs early in neurodegenerative diseases and plays a key role in axonal degeneration. Here, we provide an overview of mechanisms for regulation of axonal transport; discuss how these mechanisms are disrupted in neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, Huntington's disease, hereditary spastic paraplegia, amyotrophic lateral sclerosis, and Charcot-Marie-Tooth disease; and discuss therapeutic approaches targeting axonal transport.

Citing Articles

Axonal transport of CHMP2b is regulated by kinesin-binding protein and disrupted by CHMP2b.

Kirwan K, Puerta-Alvarado V, Waites C Life Sci Alliance. 2025; 8(5).

PMID: 40021219 PMC: 11871287. DOI: 10.26508/lsa.202402934.


Advances in Huntington's Disease Biomarkers: A 10-Year Bibliometric Analysis and a Comprehensive Review.

Aqel S, Ahmad J, Saleh I, Fathima A, Al Thani A, Mohamed W Biology (Basel). 2025; 14(2).

PMID: 40001897 PMC: 11852324. DOI: 10.3390/biology14020129.


RhoA/ROCK/GSK3β Signaling: A Keystone in Understanding Alzheimer's Disease.

Medd M, Yon J, Dong H Curr Issues Mol Biol. 2025; 47(2).

PMID: 39996845 PMC: 11854763. DOI: 10.3390/cimb47020124.


Scattering approach to diffusion quantifies axonal damage in brain injury.

Abdollahzadeh A, Coronado-Leija R, Lee H, Sierra A, Fieremans E, Novikov D ArXiv. 2025; .

PMID: 39975429 PMC: 11838777.


A Novel Histone Deacetylase 6 Inhibitor, 4-FHA, Improves Scopolamine-Induced Cognitive and Memory Impairment in Mice.

Seo J, Kim J, Ko Y, Lee B, Hur K, Jung Y Biomol Ther (Seoul). 2025; 33(2):268-277.

PMID: 39933949 PMC: 11893501. DOI: 10.4062/biomolther.2024.110.


References
1.
Du J, Wei Y, Liu L, Wang Y, Khairova R, Blumenthal R . A kinesin signaling complex mediates the ability of GSK-3beta to affect mood-associated behaviors. Proc Natl Acad Sci U S A. 2010; 107(25):11573-8. PMC: 2895136. DOI: 10.1073/pnas.0913138107. View

2.
Caviston J, Zajac A, Tokito M, Holzbaur E . Huntingtin coordinates the dynein-mediated dynamic positioning of endosomes and lysosomes. Mol Biol Cell. 2010; 22(4):478-92. PMC: 3038646. DOI: 10.1091/mbc.E10-03-0233. View

3.
Vitet H, Brandt V, Saudou F . Traffic signaling: new functions of huntingtin and axonal transport in neurological disease. Curr Opin Neurobiol. 2020; 63:122-130. DOI: 10.1016/j.conb.2020.04.001. View

4.
Onishi T, Maeda R, Terada M, Sato S, Fujii T, Ito M . A novel orally active HDAC6 inhibitor T-518 shows a therapeutic potential for Alzheimer's disease and tauopathy in mice. Sci Rep. 2021; 11(1):15423. PMC: 8322070. DOI: 10.1038/s41598-021-94923-w. View

5.
Abrahamsen G, Fan Y, Matigian N, Wali G, Bellette B, Sutharsan R . A patient-derived stem cell model of hereditary spastic paraplegia with SPAST mutations. Dis Model Mech. 2012; 6(2):489-502. PMC: 3597030. DOI: 10.1242/dmm.010884. View