Controversies over the staging of α-synuclein pathology in Parkinson’s disease

Excerpt

Parkinson’s disease (PD) is a complex disorder the aetiopathogenesis of which has remained enigmatic almost 200 years after its initial description by James Parkinson. It is now accepted that the neuropathological changes defining PD are by no means confined to the substantia nigra pars compacta but that other central and peripheral nervous tissues show degenerative changes as well, which result in dysfunction in a variety of neurotransmitter systems. The papers by Polymeropoulos et al. (15) and Kruger et al. (11), demonstrating that α-synuclein (αSyn) gene mutations can cause PD, and the discovery that the encoded protein, which is natively unfolded and still of unknown physiological function, constitutes a major component of Lewy bodies (LBs) and Lewy neurites (LNs) by Spillantini et al. [16], provided the cornerstone for a molecular definition of the disease and placed αSyn at the centre of PD research interests. …