Silencing synuclein at the synapse with PLK2
Year: 2013
Type: article
Abstract: The significance of α-synuclein (α-syn) phosphorylation to Parkinson disease (PD) pathology has been controversial since the initial identification of this posttranslational modification in intracellular Lewy bodies (1, 2). The modification of serine-129 (S129), which appears to be the most common phosphorylation site on α-syn (3, 4), has had the focus of attention. Although several different kinase families have been linked to modification of S129 in vitro, definitive in vivo evidence that a given kinase family causes the modification has been lacking (5). In addition to the lack of clarity regarding which kinases phosphorylate α-syn in a physiologically relevant context, it has been unclear whether phosphorylation of S129 is protective or harmful to neurons. The most significant problem in this regard has been that genetic manipulation of α-syn at S129—by mutation to either alanine or aspartate—has yielded varying results in cultured cells and different model organisms, including flies, worms, and rodents (5). Because the phosphorylation of S129 appeared to have no consistent effect on α-syn function in the cell, it has been unclear whether the process does anything more than reflect the magnitude of total α-syn levels in diseased neurons. In their article in PNAS, Oueslati et al. (6) now reveal a unique and unexpected effect coupled to S129 phosphorylation.
Authors: Brendan D. Looyenga, Patrik Brundin
Institutions: Van Andel Institute, Calvin University
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2016571159