Back to Search
Start Over
Back to the tubule: microtubule dynamics in Parkinson's disease.
- Source :
-
Cellular and molecular life sciences : CMLS [Cell Mol Life Sci] 2017 Feb; Vol. 74 (3), pp. 409-434. Date of Electronic Publication: 2016 Sep 06. - Publication Year :
- 2017
-
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.
- Subjects :
- Animals
Axons metabolism
Axons pathology
Cytoskeleton drug effects
Cytoskeleton genetics
Cytoskeleton metabolism
Drug Discovery
Humans
Microtubule-Associated Proteins analysis
Microtubule-Associated Proteins genetics
Microtubule-Associated Proteins metabolism
Microtubules drug effects
Microtubules genetics
Microtubules metabolism
Molecular Targeted Therapy
Mutation
Neurons metabolism
Neurons pathology
Parkinson Disease drug therapy
Parkinson Disease genetics
Parkinson Disease metabolism
Protein Processing, Post-Translational
Tubulin analysis
Tubulin genetics
Tubulin metabolism
tau Proteins analysis
tau Proteins genetics
tau Proteins metabolism
Cytoskeleton pathology
Microtubules pathology
Parkinson Disease pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1420-9071
- Volume :
- 74
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Cellular and molecular life sciences : CMLS
- Publication Type :
- Academic Journal
- Accession number :
- 27600680
- Full Text :
- https://doi.org/10.1007/s00018-016-2351-6