Cytosolic Dopamine And Synuclein Aggregation

David M. Devilbiss, Michelle E. Page and Barry D. Waterhouse

Joseph R. Mazzulli, Amanda J. Mishizen, Benoit I. Giasson, David R. Lynch, Steven A. Thomas, Akira Nakashima, Toshiharu Nagatsu, Akira Ota, and Harry Ischiropoulos

This week, Mazzulli et al. explored the possible relationship between two events that can occur in Parkinson's disease (PD): a decline in cellular dopamine concentrations and an increase in aggregates containing -synuclein. Mutations in the gene encoding -synuclein are responsible for some cases of familial PD. A number of factors can affect the initiation of synuclein fibril formation. In cell-free systems, dopamine interacts with -synuclein and inhibits fibril formation by stabilizing oligomeric -synuclein intermediates. The authors developed a cellular model system to examine this interaction. They engineered neuroblastoma cells to express either wild-type or mutant -synuclein and varying amounts of tyrosine hydroxylase, the rate-limiting enzyme in dopamine synthesis. Retinoic acid-induced differentiation of cells expressing the A53T synuclein mutant increased synuclein aggregates. Increasing intracellular dopamine inhibited the transformation of mutant -synuclein from soluble oligomers to Triton-insoluble aggregates.

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Cytosolic Dopamine And Synuclein Aggregation