The direct and indirect effects of α-synuclein on microtubule stability in the pathogenesis of Parkinson’s disease

The direct and indirect effects of α-synuclein on microtubule stability in the pathogenesis of Parkinson’s disease

Tom Carnwath,1 Raihan Mohammed,2 Daniel Tsiang3 1Department of Zoology, University of Cambridge, Cambridge, UK; 2Faculty of Medicine, University of Cambridge, Cambridge, UK; 3Faculty of Engineering, Imperial College London, London, UK Abstract: Despite decades of research, the mechanism of Parkins...

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Autores principales: Carnwath T, Mohammed R, Tsiang D
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2018
Materias:
Tubulin
Tau
Axon
Phosphorylation
Alzheimer’s Disease
Neurosciences. Biological psychiatry. Neuropsychiatry
RC321-571
Neurology. Diseases of the nervous system
RC346-429
Acceso en línea:https://doaj.org/article/7677ef6deb244a328ff0926bc32520bf
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spelling oai:doaj.org-article:7677ef6deb244a328ff0926bc32520bf2021-12-02T00:03:55ZThe direct and indirect effects of α-synuclein on microtubule stability in the pathogenesis of Parkinson’s disease1178-2021https://doaj.org/article/7677ef6deb244a328ff0926bc32520bf2018-06-01T00:00:00Zhttps://www.dovepress.com/the-direct-and-indirect-effects-of-alpha-synuclein-on-microtubule-stab-peer-reviewed-article-NDThttps://doaj.org/toc/1178-2021Tom Carnwath,1 Raihan Mohammed,2 Daniel Tsiang3 1Department of Zoology, University of Cambridge, Cambridge, UK; 2Faculty of Medicine, University of Cambridge, Cambridge, UK; 3Faculty of Engineering, Imperial College London, London, UK Abstract: Despite decades of research, the mechanism of Parkinson’s disease pathogenesis remains unclear. Studies have focused heavily on the protein α-synuclein, which is the primary component of Lewy bodies, the pathologic inclusions that are the hallmark of Parkinson’s on the cellular level. While the roles of α-synuclein in causing mitochondrial dysfunction and disruptions to the proteasomal system have been well documented, recently, its role in effecting microtubule dynamics has been investigated as a potential source of pathogenicity. Here, we evaluate the evidence for and against the role of α-synuclein in destabilizing microtubules, causing axonal transport deficits and eventually neurodegeneration. We present evidence for a model where α-synuclein has both a direct and indirect effect on microtubule stability. Directly, it may act as a microtubule-associated protein, binding to microtubules and directly effecting their dynamics. Indirectly, it may promote the hyperphosphorylation of the microtubule stabilizing protein, tau, leading to tau aggregation with other microtubule stabilizing proteins, hence indirectly causing microtubule destabilization. This model provides insights into the function of α-synuclein and tau in Parkinson’s disease pathogenesis and raises the possibility that this role that may also be conserved in Alzheimer’s disease. Keywords: tubulin, tau, axon, phosphorylation, Alzheimer’s diseaseCarnwath TMohammed RTsiang DDove Medical PressarticleTubulinTauAxonPhosphorylationAlzheimer’s DiseaseNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429ENNeuropsychiatric Disease and Treatment, Vol Volume 14, Pp 1685-1695 (2018)
institution DOAJ
collection DOAJ
language EN
topic Tubulin
Tau
Axon
Phosphorylation
Alzheimer’s Disease
Neurosciences. Biological psychiatry. Neuropsychiatry
RC321-571
Neurology. Diseases of the nervous system
RC346-429
spellingShingle Tubulin
Tau
Axon
Phosphorylation
Alzheimer’s Disease
Neurosciences. Biological psychiatry. Neuropsychiatry
RC321-571
Neurology. Diseases of the nervous system
RC346-429
Carnwath T
Mohammed R
Tsiang D
The direct and indirect effects of α-synuclein on microtubule stability in the pathogenesis of Parkinson’s disease
description Tom Carnwath,1 Raihan Mohammed,2 Daniel Tsiang3 1Department of Zoology, University of Cambridge, Cambridge, UK; 2Faculty of Medicine, University of Cambridge, Cambridge, UK; 3Faculty of Engineering, Imperial College London, London, UK Abstract: Despite decades of research, the mechanism of Parkinson’s disease pathogenesis remains unclear. Studies have focused heavily on the protein α-synuclein, which is the primary component of Lewy bodies, the pathologic inclusions that are the hallmark of Parkinson’s on the cellular level. While the roles of α-synuclein in causing mitochondrial dysfunction and disruptions to the proteasomal system have been well documented, recently, its role in effecting microtubule dynamics has been investigated as a potential source of pathogenicity. Here, we evaluate the evidence for and against the role of α-synuclein in destabilizing microtubules, causing axonal transport deficits and eventually neurodegeneration. We present evidence for a model where α-synuclein has both a direct and indirect effect on microtubule stability. Directly, it may act as a microtubule-associated protein, binding to microtubules and directly effecting their dynamics. Indirectly, it may promote the hyperphosphorylation of the microtubule stabilizing protein, tau, leading to tau aggregation with other microtubule stabilizing proteins, hence indirectly causing microtubule destabilization. This model provides insights into the function of α-synuclein and tau in Parkinson’s disease pathogenesis and raises the possibility that this role that may also be conserved in Alzheimer’s disease. Keywords: tubulin, tau, axon, phosphorylation, Alzheimer’s disease
format article
author Carnwath T
Mohammed R
Tsiang D
author_facet Carnwath T
Mohammed R
Tsiang D
author_sort Carnwath T
title The direct and indirect effects of α-synuclein on microtubule stability in the pathogenesis of Parkinson’s disease
title_short The direct and indirect effects of α-synuclein on microtubule stability in the pathogenesis of Parkinson’s disease
title_full The direct and indirect effects of α-synuclein on microtubule stability in the pathogenesis of Parkinson’s disease
title_fullStr The direct and indirect effects of α-synuclein on microtubule stability in the pathogenesis of Parkinson’s disease
title_full_unstemmed The direct and indirect effects of α-synuclein on microtubule stability in the pathogenesis of Parkinson’s disease
title_sort direct and indirect effects of α-synuclein on microtubule stability in the pathogenesis of parkinson’s disease
publisher Dove Medical Press
publishDate 2018
url https://doaj.org/article/7677ef6deb244a328ff0926bc32520bf
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