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 oil 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. (c) 2007 Elsevier Inc. All rights reserved.