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08:09

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Published on: January 7, 2014

Microtubule alterations occur early in experimental parkinsonism and the microtubule stabilizer epothilone D is

Daniele Cartelli1, Francesca Casagrande, Carla Letizia Busceti

  • 1Department of Biosciences, Università degli Studi di Milano, Milan, Italy.

Scientific Reports
|May 15, 2013
PubMed

Insights

Microtubule (MT) dysfunction is an early event in Parkinson's disease, preceding neurodegeneration. Stabilizing MTs with Epothilone D protected against MPTP-induced damage, suggesting a therapeutic strategy.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Neurodegenerative Diseases

Background:

  • Microtubule (MT) dysfunction is implicated in Parkinson's disease (PD) pathogenesis.
  • The precise timing of MT alterations relative to neurodegeneration remains unclear.

Purpose of the Study:

  • To determine if MT stability changes precede axonal transport defects and neurite degeneration in MPTP-induced experimental parkinsonism.
  • To investigate the therapeutic potential of MT stabilization in PD.

Main Methods:

  • MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) was administered to C57Bl mice to induce experimental parkinsonism.
  • Assessed mitochondrial distribution, cytoskeletal proteins, and MT stability.
  • Evaluated the effect of Epothilone D, a MT stabilizer, on MPTP-induced neurodegeneration.

Main Results:

  • MPTP induced time- and dose-dependent alterations in mitochondrial distribution and MT stability.
  • Increased neuron-specific βIII tubulin and deTyr tubulin were observed in dopaminergic neurons.
  • Epothilone D treatment rescued MT defects and attenuated nigrostriatal neurodegeneration.

Conclusions:

  • MT alterations are an early event specifically linked to dopaminergic neuron degeneration in experimental parkinsonism.
  • Pharmacological stabilization of MTs represents a promising therapeutic strategy for managing Parkinson's disease.

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