Serine-129 phosphorylation of α-synuclein is an activity-dependent trigger for physiologic protein-protein interactions and synaptic function

Authors: Leonardo A. Parra-Rivas, Kayalvizhi Madhivanan, Brent D. Aulston, Lina Wang, Dube Dheeraj Prakashchand, Nicholas P. Boyer, Veronica M. Saia-Cereda, Kristen Branes-Guerrero, Donald P. Pizzo, Pritha Bagchi, V.S. Sundar, Yong Tang, Utpal Das, David A. Scott, Padmini Rangamani, Yuki Ogawa, and Subhojit Roy

Neuron,  December 20, 2023

Researchers investigate the pathogenesis of Parkinson’s disease and related synucleinopathies using Axion’s Maestro MEA and other methods.

The phosphorylation of α-synuclein at the serine-129 site (α-syn serine-129) serves as a marker for Parkinson’s disease and similar conditions but scientists are calling its strictly pathogenic role into question. In this study researchers use a multiplatform approach, including multielectrode array (MEA) recordings on Axion’s noninvasive Maestro MEA platform, to investigate the role of α-syn serine-129 phosphorylation in the brain. Overall, the authors conclude that their experiments “support a physiologic role for α-syn Ser129P at synapses, advocating a model where activity-induced Ser129P triggers the interaction of α-syn with a network of synaptic proteins that eventually leads to physiologic attenuation of neurotransmitter release,” and suggest that these findings may have important implications for disease research and therapeutic development.