Modeling Pathogenesis of Huntington’s Disease with Inducible Neuroprogenitor Cells
| Autor: | Khosrow Rezvani, J. M. Ferguson, Gaofeng Dong, A. J. Duling, Hongmin Wang, Dong Zhang, Mervyn J. Monteiro, Xiao-Jiang Li, Shengyun Fang, Shihua Li, R. G. Nicholas |
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| Rok vydání: | 2011 |
| Předmět: |
congenital
hereditary and neonatal diseases and abnormalities Programmed cell death Huntingtin Green Fluorescent Proteins Nerve Tissue Proteins Biology medicine.disease_cause Models Biological Article Cell Line Pathogenesis Cellular and Molecular Neuroscience Exon Neural Stem Cells Huntington's disease mental disorders Neurites medicine Animals Protein Structure Quaternary Cellular Senescence Wild type Exons Cell Biology General Medicine medicine.disease Molecular biology Rats Oxidative Stress Huntington Disease Cell culture Nerve Degeneration Mutant Proteins Oxidative stress |
| Zdroj: | Cellular and Molecular Neurobiology. 31:737-747 |
| ISSN: | 1573-6830 0272-4340 |
| DOI: | 10.1007/s10571-011-9679-0 |
| Popis: | Huntington’s disease (HD) is caused by an abnormal expansion of CAG trinucleotide repeats encoding polyglutamine (polyQ) in the first exon of the huntingtin (htt) gene. Despite considerable efforts, the pathogenesis of Huntington’s disease (HD) remains largely unclear due to a paucity of models that can reliably reproduce the pathological characteristics of HD. Here, we report a neuronal cell model of HD using the previously established tetracycline regulated rat neuroprogenitor cell line, HC2S2. Stable expression of enhanced green fluorescence protein (EGFP) tagged-htt exon 1 (referred to as 28Q and 74Q, respectively) in the HC2S2 cells did not affect rapid neuronal differentiation. However, compared to the cells expressing wild type htt, the cell line expressing mutant htt showed an increase in time-dependent cell death and neuritic degeneration, and displayed increased vulnerability to oxidative stress. Increased protein aggregation during the process of neuronal aging or when the cells were exposed to oxidative stress reagents was detected in the cell line expressing 74Q but not in its counterpart. These results suggest that the neuroprogenitor cell lines mimic the major neuropathological characteristics of HD and may provide a useful tool for studying the neuropathogenesis of HD and for high-throughput screening of therapeutic compounds. |
| Databáze: | OpenAIRE |
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