(controversy surrounding L-dopa continues
Evidence for Dopamine Toxicity in Neurodegeneration

Linan Chen, Yunmin Ding, Barbara Cagniard, Amber D. Van Laar, Amanda Mortimer, Wanhao Chi, Teresa G. Hastings, Un Jung Kang, and Xiaoxi Zhuang

The symptoms of Parkinson's disease are caused by loss of dopaminergic neurons in the substantia nigra; therefore, it seems somewhat counterintuitive that dopamine may be a vulnerability factor in the disease. But Chen et al. now provide strong evidence for this hypothesis. Dopamine metabolites are highly reactive species that cause oxidative damage, leading ultimately to degeneration. Dopaminergic neurons sequester dopamine into vesicles, thus protecting these cells from damage. To examine the potential toxic effects of dopamine, Chen et al. engineered transgenic mice to conditionally express the dopamine transporter (DAT) in striatal neurons: targets of dopaminergic neurons that lack the ability to sequester dopamine. When DAT was turned on, the mice exhibited motor dysfunction and neurodegeneration within weeks. These effects depended on the presence of dopamine: if the dopaminergic inputs to the striatum were unilaterally severed, motor function on the contralateral side was spared. In contrast, L-DOPA accelerated neurodegeneration.

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Article adapted by Medical News Today from original press release.