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FEBS Lett. 2005 Feb 14;579(5):1197-202. Epub 2005 Jan 21.

L-dopa and dopamine enhance the formation of aggregates under proteasome inhibition in PC12 cells.

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Department of Neurology, Institute of Neurological Sciences, Faculty of Medicine, Tottori University, 36-1, Nishicho, Yonago 683-8504, Japan.


The formation of inclusion bodies in dopaminergic neurons is associated with the pathogenesis of Parkinson's disease. In order to clarify the role of dopamine/L-dopa in the formation of protein aggregates, we investigated dopamine/L-dopa-related aggregation using an experimental inclusion model. The inhibition of tyrosine hydroxylase (TH) by alpha-methyltyrosine dramatically decreased MG132-induced aggregate formation. In addition, the inhibition of TH caused the upregulation of proteasomes in cultured cells and the dopamine/L-dopa induced non-enzymatic polymerization of ubiquitin. This inhibition did not affect cell viability. These results suggest that dopamine/L-dopa might enhance aggregate formation, and that intracellular aggregates may not be toxic to cells.

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