Fig. 1

Physiologic vs. pathologic αS serine-129 phosphorylation (pS129). Top, Lewy bodies and Lewy neurites are strongly S129-phosphorylated. Bottom, dynamic physiological pS129 finetunes synaptic transmission. αS undergoes cycles of phosphorylation and de-phosphorylation as well as membrane attachment and detachment. Membrane-associated αS is preferentially phosphorylated. fPD-linked αS mutations and proteasomal inhibition perturb pS129 dynamics (indicated by thunderbolt). The relationship (if any) between perturbation of pS129 at the synapse and phosphorylation in Lewy lesions requires further research (dotted lines). Created with BioRender.com.