A conversation featuring Associate Editor Paul Fraser and co-authors Dennis Selkoe and Ulf Dettmer from Harvard
March 10, 2014 — In the last of our four-part podcast series on the best articles of 2013 in the The Journal of Biological Chemistry, we hear about the debate surrounding α-synuclein, which plays a critical role in Parkinson’s disease. Is it an unfolded monomer? Is it a helically-folded tetramer? Paul Fraser, a professor of medical biophysics at the University of Toronto and a JBC associate editor, speaks with Dennis Selkoe, a professor of neurological diseases at Harvard Institutes of Medicine, and Ulf Dettmer, a research fellow in neurology also at Harvard. Selkoe and Dettmer are co-authors of JBC’s best article of 2013 in the Affinity category of Cell Biology. It is titled, “In Vivo Cross-linking Reveals Principally Oligomeric Forms of α-Synuclein and β-Synuclein in Neurons and Non-neural Cells,” and it was published in March. The paper details a new method for cross-linking α-synuclein in living cells that reveals a form consistent with a tetramer. In this conversation, we hear about the prior research leading to this article and what to look forward to as the debate continues.
In Vivo Cross-linking Reveals Principally Oligomeric Forms of α-Synuclein and β-Synuclein in Neurons and Non-neural Cells
Background: αSyn is central to Parkinsonism, but its native state is unsettled.
Results: A new, facile method for cross-linking αSyn in living cells, including neurons, reveals a major 60-kDa form consistent with a tetramer. Cell lysis destabilizes it, yielding mostly monomers.
Conclusion: αSyn exists principally as a metastable tetramer in vivo.
Significance: Models of native αSyn as an unfolded monomer should be reconsidered.
Click here to read a transcript of this podcast interview.