Impairment of microtubule system increases alpha-synuclein aggregation and toxicity

Biochem Biophys Res Commun. 2008 Jan 25;365(4):628-35. doi: 10.1016/j.bbrc.2007.11.020. Epub 2007 Nov 20.


The accumulation of fibrillar form of alpha-synuclein (alpha-syn) has been implicated in Parkinson's disease. Here we show that tubulin can stimulate alpha-syn fibrillization in vitro in different ways depending on its oligomeric status. The physiological significance of tubulin-seeded alpha-syn fibrillization is demonstrated by using Saccharomyces cerevisiae as a model system. Perturbation of microtubule system either by treating benomyl that inhibits microtubule assembly or by deleting genes involved in microtubule biogenesis, stimulates alpha-syn aggregation and toxicity. These results suggest that impairment of the microtubule system may act as a risk factor deteriorating the alpha-syn-mediated neurodegeneration by increasing the chance of tubulin-seeded alpha-syn aggregation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Microtubules / drug effects
  • Microtubules / metabolism*
  • Microtubules / ultrastructure
  • Saccharomyces cerevisiae / cytology*
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / physiology*
  • Tubulin / administration & dosage*
  • alpha-Synuclein / metabolism*


  • Tubulin
  • alpha-Synuclein