The term alpha-synucleinopathy is used to name a group of disorders having in 
common the abnormal deposition of alpha-synuclein in the cytoplasm of neurons or 
glial cells, as well as in extracellular deposits of amyloid. In Parkinson's 
disease and Lewy body dementia, alpha-synuclein is the main component of Lewy 
bodies and dystrophic neurites; alpha-synuclein also accumulates in the 
cytoplasm of glial cells. In multiple system atrophy, alpha-synuclein conforms 
the cytoplasmic oligodendroglial inclusions and the neuronal inclusions which 
are the hallmark of this disease. Finally, the amyloidogenic fragment 61-95 
amino acids of alpha-synuclein is the non-Abeta component of senile plaque 
amyloid in Alzheimer disease. Accumulations of alpha-synuclein in all these 
disorders have in common a fibrilar configuration, but they differ in the 
binding of alpha-synuclein to distinct proteins with the exception of ubiquitin 
whose binding to alpha-synuclein is common to all alpha-synuclein inclusions. 
The mechanisms leading to alpha-synuclein fragmentation and aggegation into 
extracellular amyloid are not known, although alpha-synuclein fragment and 
betaA4 aggregates are the result of abnormal cleavage of large precursors. On 
the other hand, several studies have shown that alpha-synuclein may adopt a 
fibrilar conformation and give rise to insoluble forms and high molecular weight 
aggregates in vitro. Similar complexes have also been observed in 
alpha-synucleinopathies. Although studies in vitro and in vivo have shown toxic 
effects of alpha-synuclein, the consequence of alpha-synuclein deposition on 
cell survival in alpha-synucleinopathies is not known.