Impairment of microtubule system increases alpha-synuclein aggregation and toxicity.
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.
Kim
Myunghye
M
School of Chemical and Biological Engineering, Seoul National University, 599 Gwanangno, Gwanak-gu, Seoul 151-744, Republic of Korea.
Jung
Wonsuk
W
Lee
In-Hwan
IH
Bhak
Ghibom
G
Paik
Seung R
SR
Hahn
Ji-Sook
JS
D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D014404:Tubulin / Q000008:administration & dosage*; D051844:alpha-Synuclein / Q000378:metabolism*
D014404:Tubulin; D051844:alpha-Synuclein