α-Synuclein is a key protein implicated in a broad class of neurodegenerative disorders termed “synucleinopathies,” including Parkinson’s disease and dementia with Lewy bodies. It is also an abundant presynaptic protein whose physiological role in neurotransmission is underappreciated. I’ll discuss our latest findings on the dynamic physiological states of α-synuclein, focusing on phospho-serine129 (pS129). This post-translationally modified form has been regarded exclusively as a surrogate marker of pathology. Intriguingly, our results imply that pS129 is physiologically triggered by neuronal activity to positively regulate neurotransmission.

Ann Romney Center for Neurologic Diseases

Brigham and Women’s Hospital & Harvard Medical School

Boston, USA