The Discovery of α‐Synuclein in Lewy Pathology of Parkinson's Disease: The Inspiration of a Revolution

When tasked with selecting one of the most influential papers in the field since the 1950s, Spillantini et al 1 describing the presence of α-synuclein (aSyn) in Lewy bodies (LBs) in Parkinson's disease (PD) was our clear first choice.Following James Parkinson's description of the Shaking Palsy in 1817, progress in understanding PD mirrored the slowness of movement that characterizes the disease itself.Almost 100 years later, in 1912, Friedrich Lewy described the inclusion bodies we now recognize as the pathological hallmark of PD and a further 85 years later, investigation of the Contursi kindred, manifesting autosomal dominant PD, identified a causative single base mutation in SNCA. 2 It took just 2 months for Spillantini and colleagues to publish their landmark paper describing the presence of aSyn in LBs in idiopathic PD and dementia with Lewy bodies (DLB).In the 24 years since this short paper was published (Spillantini et al's article was less than half the length of this Viewpoint), it has catalyzed numerous advances in understanding the pathophysiology of synucleinopathies, amassing over 2,225 citations and influencing almost every aspect of research in PD and other neurodegenerative disorders.