Mutant a-Synucleins And Cytosolic Catecholamines

Main Category: Parkinson's Disease
Also Included In: Neurology / Neuroscience
Article Date: 09 Sep 2006 - 9:00 PDT

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Parkinson's disease (PD) is caused by the demise of dopamine neurons. This week, Mosharov et al. probe the role of a-synuclein, a protein mutated in some patients with PD and a major component of the telltale Lewy bodies. The authors used intracellular patch electrochemistry to specifically determine the cytosolic concentrations of catecholamines in adrenal chromaffin cells and L-DOPA-treated PC12 cells. Overexpression of wild-type or mutant a-synucleins increased cytosolic catecholamine concentrations to levels that could overwhelm the capacity of neurons to buffer against the oxyradicals produced by dopamine oxidation. Addition of α-synucleins to isolated chromaffin granules disrupted the vesicular pH gradient, indicating that the observed increase in cytosolic catecholamine resulted from the leaking of neurotransmitter from vesicles. Mutant a-synucleins produced a greater increase in cytosolic neurotransmitter than their wild-type counterpart, possibly because of their propensity to produce membrane-damaging protofibrils.

Eugene V. Mosharov, Roland G. W. Staal, Jordi Bove, Delphine Prou, Anthonia Hananiya, Dmitriy Markov, Nathan Poulsen, Kristin E. Larsen, Candace M. H. Moore, Matthew D. Troyer, Robert H. Edwards, Serge Przedborski, and David Sulzer

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