Inclusion Body Formation and Apoptotic Cell Death in the Human Neural Stem Cells HB1.F3 Following Gene Transfection of Alpha-Synuclein and Synphilin-1.
- Author:
Sang Myung CHEON
1
;
Gwang LEE
;
Jae Woo KIM
;
Seung Up KIM
Author Information
1. Department of Neurology, College of Medicine, Dong-A University, Busan, Korea. jwkim@mail.donga.ac.kr
- Publication Type:Original Article
- Keywords:
Parkinson's disease;
Alpha-synuclein;
Lewybody;
Levodopa;
Apoptosis
- MeSH:
alpha-Synuclein*;
Apoptosis;
Cell Death*;
Humans*;
Inclusion Bodies*;
Levodopa;
Lewy Bodies;
Models, Genetic;
Neural Stem Cells*;
Neurons;
Parkinson Disease;
Transfection*;
Tyrosine 3-Monooxygenase
- From:Journal of the Korean Neurological Association
2007;25(3):344-352
- CountryRepublic of Korea
- Language:Korean
-
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.
