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Exogenous Administration of Microsomes-associated Alpha-synuclein Aggregates to Primary Neurons As a Powerful Cell Model of Fibrils Formation
Published on: June 26, 2018
Impairment of microtubule system increases alpha-synuclein aggregation and toxicity
Myunghye Kim1, Wonsuk Jung, In-Hwan Lee
1School of Chemical and Biological Engineering, Seoul National University, 599 Gwanangno, Gwanak-gu, Seoul 151-744, Republic of Korea.
Abstract:
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.
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