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Back to the tubule: microtubule dynamics in Parkinson's disease

Pellegrini, L; Wetzel, A; Grannó, S; Heaton, G; Harvey, K; (2017) Back to the tubule: microtubule dynamics in Parkinson's disease. Cellular and Molecular Life Sciences , 74 (3) pp. 409-434. 10.1007/s00018-016-2351-6. Green open access

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Abstract

Cytoskeletal homeostasis is essential for the development, survival and maintenance of an efficient nervous system. Microtubules are highly dynamic polymers important for neuronal growth, morphology, migration and polarity. In cooperation with several classes of binding proteins, microtubules regulate long-distance intracellular cargo trafficking along axons and dendrites. The importance of a delicate interplay between cytoskeletal components is reflected in several human neurodegenerative disorders linked to abnormal microtubule dynamics, including Parkinson's disease (PD). Mounting evidence now suggests PD pathogenesis might be underlined by early cytoskeletal dysfunction. Advances in genetics have identified PD-associated mutations and variants in genes encoding various proteins affecting microtubule function including the microtubule-associated protein tau. In this review, we highlight the role of microtubules, their major posttranslational modifications and microtubule associated proteins in neuronal function. We then present key evidence on the contribution of microtubule dysfunction to PD. Finally, we discuss how regulation of microtubule dynamics with microtubule-targeting agents and deacetylase inhibitors represents a promising strategy for innovative therapeutic development.

Type: Article
Title: Back to the tubule: microtubule dynamics in Parkinson's disease
Location: Switzerland
Open access status: An open access version is available from UCL Discovery
DOI: 10.1007/s00018-016-2351-6
Publisher version: http://doi.org/10.1007/s00018-016-2351-6
Language: English
Additional information: © The Author(s) 2016. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
Keywords: Axonal transport, Cytoskeleton, LRRK2, Microtubule dynamics, Microtubule targeting agents, PARK genes, Parkinson’s disease, Tau, Wnt signalling
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmacology
URI: https://discovery.ucl.ac.uk/id/eprint/1515926
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