Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2017 Sep:105:328-335.
doi: 10.1016/j.nbd.2016.12.021. Epub 2016 Dec 22.

Altered microtubule dynamics in neurodegenerative disease: Therapeutic potential of microtubule-stabilizing drugs

Kurt R Brunden  1 , Virginia M-Y Lee  2 , Amos B Smith 3rd  3 , John Q Trojanowski  2 , Carlo Ballatore  4
Affiliations
Review

Altered microtubule dynamics in neurodegenerative disease: Therapeutic potential of microtubule-stabilizing drugs

Kurt R Brunden et al. Neurobiol Dis. 2017 Sep.

Abstract

Many neurodegenerative diseases are characterized by deficiencies in neuronal axonal transport, a process in which cellular cargo is shuttled with the aid of molecular motors from the cell body to axonal termini and back along microtubules (MTs). Proper axonal transport is critical to the normal functioning of neurons, and impairments in this process could contribute to the neuronal damage and death that is characteristic of neurodegenerative disease. Although the causes of axonal transport abnormalities may vary among the various neurodegenerative conditions, in many cases it appears that the transport deficiencies result from a diminution of axonal MT stability. Here we review the evidence of MT abnormalities in a number of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and traumatic brain injury, and highlight the potential benefit of MT-stabilizing agents in improving axonal transport and nerve function in these diseases. Moreover, we discuss the challenges associated with the utilization of MT-stabilizing drugs as therapeutic candidates for neurodegenerative conditions.

Keywords: Alzheimer; Amyotrophic lateral sclerosis; Axons; Frontotemporal lobar degeneration; Microtubules; Neurodegeneration; Parkinson; Transport; Traumatic brain injury.

PubMed Disclaimer

Figures

Figure 1
Figure 1
A. Schematic representation of the complex between tau (drawn in green) and a MT, as well as B. the structure of the six human tau isoforms.
See this image and copyright information in PMC

References

    1. Alonso AD, et al. Abnormal phosphorylation of tan and the mechanism of Alzheimer neurofibrillary degeneration: Sequestration of microtubule-associated proteins 1 and 2 and the disassembly of microtubules by the abnormal tau. Proceedings of the National Academy of Sciences of the United States of America. 1997;94:298–303. - PMC - PubMed
    1. Alonso AD, et al. Abnormally phosphorylated-tau from Alzheimer-disease brain depolymerizes microtubules. Neurobiology of Aging. 1994;15:S37–S37.
    1. Amos LA. Microtubule structure and its stabilisation. Org Biomol Chem. 2004;2:2153–2160. - PubMed
    1. Arriagada PV, et al. Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimers disease. Neurology. 1992;42:631–639. - PubMed
    1. Baldwin KR, et al. Axonal transport defects are a common phenotype in Drosophila models of ALS. Hum Mol Genet. 2016 - PMC - PubMed

MeSH terms

Substances