Affordable Access

Publisher Website

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

  • Carnwath, T
  • Mohammed, R
  • Tsiang, D
Publication Date
Apr 04, 2018
DOI: 10.2147/NDT.S166322
Spiral - Imperial College Digital Repository


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.

Report this publication


Seen <100 times