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

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 alp ha-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 inc lusions 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. J Korean Neurol Assoc 25(3):344-352, 2007