The α‐Synucleinopathies: Parkinson's Disease, Dementia with Lewy Bodies, and Multiple System Atrophy

A bstract : Parkinson's disease is the second most common neurodegenerative disease, after Alzheimer's disease. Neuropathologically, it is characterized by the degeneration of populations of nerve cells that develop filamentous inclusions in the form of Lewy bodies and Lewy neurites. Recent work has shown that the filamentous inclusions of Parkinson's disease are made of the protein α‐synuclein and that rare, familial forms of Parkinson's disease are caused by missense mutations in the α‐synuclein gene. Besides Parkinson's disease, the filamentous inclusions of two additional neurodegenerative diseases, namely, dementia with Lewy bodies and multiple system atrophy, have also been found to be made of α‐synuclein. Recombinant α‐synuclein has been shown to assemble into filaments with similar morphologies to those found in the human diseases and with a cross‐β fiber diffraction pattern. The new work has established the α‐synucleinopathies as a major class of neurodegenerative disease.