Parkinson's Disease Research Today is a free monthly online journal that collates and summarizes the latest research about Parkinson's Disease, including details on symptoms, treatment, genetics, medication.

Dopamine differentially induces aggregation of A53T mutant and wild type alpha-synuclein: insights into the protein chemistry of Parkinson's disease.

Moussa CE, Mahmoodian F, Tomita Y, Sidhu A

Department of Biochemistry, Molecular and Cell Biology, and Georgetown University, Washington, DC 20007, USA.

Aggregation of alpha-synuclein is known to be a causal factor in the genesis of Parkinson's disease and Dementia with Lewy bodies. Duplication and/or triplication and mutation of the alpha-synuclein gene are associated with sporadic and familial Parkinson's disease. Synucleinopathies appear to primarily affect dopaminergic neurons. The present studies investigate the role of dopamine in alpha-synuclein aggregation through NMR. Dopamine causes aggregation of both wild type and A53T mutant alpha-synuclein in a temperature-dependent manner, but the mutant A53T shows a greater propensity to aggregate in the presence of dopamine only at 37 degrees C. A single point mutation in the alpha-synuclein A53T mutant gene results in a structural change in the protein and drastically increases its propensity to aggregate in the presence of dopamine. The present data indicate that mutation in the alpha-synuclein gene may predispose the protein to dopamine-induced aggregation, thereby contributing to disease pathogenesis.

Published 17 December 2007 in Biochem Biophys Res Commun, 365(4): 833-9.
Full-text of this article is available online (may require subscription).

© 2004-2008 Parkinson's Disease Research Today. All Rights Reserved.