Alpha Synuclein, cellular dysfunction and Parkinson disease

National Institute On Aging

Investigators

Linked publications, trials & patents

Abstract

Our current work has focussed on the role of alpha synuclein phosphorylation in cells and tissue. In mouse models, we have shown using imaging spatial transcriptomics that the cells that have greatest amount of phosphorylated synuclein tend to have higher expression of the stress responsive kinase Plk2. The combination of high Plk2 and phosphorylated alpha synuclein is particularly high in excitatory neurons, particularly layer 5 extratelencephalic cells. We have also found that there is a positive relationship between neuronal activity and level of phosphorylation of alpha synuclein in cells without pathology and that blocking phosphorylation via a Plk2 inhibitor also changes neuronal electrical activity. Current work is being performed to see if the same effects are seen in human iPSC-derived neurons.