A common finding in many neurodegenerative diseases is the presence of inclusion 
bodies made of aggregated proteins in neurons of affected brain regions. In 
Parkinson's disease, the inclusion bodies are referred to as Lewy bodies and 
their main component is alpha-synuclein. Although many studies have suggested 
that inclusion bodies may be cell protective, it is still not clear whether Lewy 
bodies promote or inhibit dopaminergic cell death in Parkinson's disease. 
Synphilin-1 interacts with alpha-synuclein and is present in Lewy bodies. 
Accumulation of ubiquitylated synphilin-1 leads to massive formation of 
inclusion bodies, which resemble Lewy bodies by their ability to recruit 
alpha-synuclein. We have recently isolated an isoform of synphilin-1, 
synphilin-1A, that spontaneously aggregates in cells, and is present in 
detergent-insoluble fractions of brain protein samples from 
alpha-synucleinopathy patients. Synphilin-1A displays marked neuronal toxicity 
and, upon proteasome inhibition, accumulates into ubiquitylated inclusions with 
concomitant reduction of its intrinsic toxicity. The fact that alpha-synuclein 
interacts with synphilin-1A, and is recruited to synphilin-1A inclusion bodies 
in neurons together with synphilin-1, further indicates that synphilin-1A cell 
model is relevant for research on Parkinson's disease. Synphilin-1A cell model 
may help provide important insights regarding the role of inclusion bodies in 
Parkinson's disease and other neurodegenerative disorders.