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

J Korean Neurol Assoc > Volume 25(3); 2007 > Article

Journal of the Korean Neurological Association 2007;25(3): 344-352.

인간 신경 줄기세포 HB1.F3에서 alpha-synuclein과 synphilin-1 유전자 전이를 통한 봉입체 형성과 세포 자멸사

천상명, 이 광a 김재우 김승업a

동아대학교 의과대학 신경과, 아주대학교 뇌질환 연구센터a

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

Sang-Myung Cheon

Department of Neurology, College of Medicine, Dong-A University, Busan; Brain Disease Research Center, Ajou Universitya, Suwon, Korea

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. KeyWords:Parkinson’s disease, Alpha-synuclein, Lewybody, Levodopa, Apoptosis