The direct and indirect effects of α-synuclein on microtubule stability in the pathogenesis of Parkinson’s disease
File(s)
Author(s)
Carnwath, Tom
Mohammed, Raihan
Tsiang, Daniel
Type
Journal Article
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 pathological 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 a 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.
Date Issued
2018-06-27
Date Acceptance
2018-04-04
Citation
Neuropsychiatric Disease and Treatment, 2018, 2018 (14), pp.1685-1695
ISSN
1176-6328
Publisher
Dove Medical Press
Start Page
1685
End Page
1695
Journal / Book Title
Neuropsychiatric Disease and Treatment
Volume
2018
Issue
14
Copyright Statement
© 2018 The Author(s). This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.
Subjects
Science & Technology
Life Sciences & Biomedicine
Clinical Neurology
Psychiatry
Neurosciences & Neurology
tubulin
tau
axon
phosphorylation
Alzheimer's disease
TAU-PHOSPHORYLATION
HYPERPHOSPHORYLATED TAU
ALZHEIMERS-DISEASE
AXONAL-TRANSPORT
DESTABILIZATION
POLYMERIZATION
AGGREGATION
ACTIVATION
REDUCTION
PATHOLOGY
Alzheimer’s disease
1103 Clinical Sciences
1109 Neurosciences
Neurology & Neurosurgery
Publication Status
Published