Inclusion Body Formation and Apoptotic Cell Death in the Human Neural Stem Cells HB1.F3 Following Gene Transfection of Alpha-Synuclein and Synphilin-1

Abstract

Background:The etiology of Parkinson’s disease (PD) has not been established, but familial forms of the disease

have some clues for its pathogenesis. Autosomal dominantly inherited familial PD induced by aberrations of the

alpha-synucein gene has been known as a genetic model of PD and sheds light to the understanding of PD

pathogenesis. Synphilin-1 is a protein which interacts with alpha-synuclein and constitutes the Lewy body.

Methods:Immortalized human neural stem cells were transfected with the alpha-synuclein gene and synphilin-1

gene, to define the role of Lewy body inclusions in neuronal cell death.

Results:Human neural stem cells with Lewy body-like inclusions showed an increased apoptotic cell death

compared to those with diffuse alpha-synuclein-positive and synphilin-1-positive reaction after transfection with

the alpha-synuclein gene and synphilin-1 gene. Tyrosine hydroxylase over-expressing cells produced a high level

of levodopa and showed a higher rate of the apoptotic marker.

Conclusions:These results suggest that the formation of Lewy body-like inclusions by the over-expression of

alpha-synuclein and synphilin-1 could be an underlying cause of apoptotic neuronal cell death and the dopaminergic cell might be more susceptible.