The study of dopamine metabolism with LRRK2 variants in Parkinson’s disease
Background: Parkinson's disease (PD) is a neurodegenerative disease in which symptoms typically appear when a loss of dopaminergic (DA) neurons causes dopamine levels to fall significantly. Leucine rich repeat kinase 2 (LRRK2) gene mutations are the most common genetic cause of PD. Dopamine dec...
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| Format: | Final Year Project (FYP) |
| Language: | English |
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2015
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| Online Access: | http://hdl.handle.net/10356/65657 |
| _version_ | 1826122440222179328 |
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| author | Kwok, Wei Hao |
| author2 | Zhao Yi |
| author_facet | Zhao Yi Kwok, Wei Hao |
| author_sort | Kwok, Wei Hao |
| collection | NTU |
| description | Background: Parkinson's disease (PD) is a neurodegenerative disease in which symptoms typically appear when a loss of dopaminergic (DA) neurons causes dopamine levels to fall significantly. Leucine rich repeat kinase 2 (LRRK2) gene mutations are the most common genetic cause of PD. Dopamine decarboxylase (DDC) and dopamine beta hydroxylase (DBH) are critical enzymes involved in dopamine metabolism. Previous gene expression profiling have revealed that DDC and DBH were downregulated in LRRK2-G2019S variant stable transfected cell lines in comparison with wild type LRRK2. Approach: In this study, the dopamine metabolism in stable transfected SH-SY5Y cell lines and Drosophila models were investigated. Real-time polymerase chain reaction (PCR), high performance liquid chromatography (HPLC) and cell morphology test were used for the study. Results: The results confirmed that DDC and DBH were downregulated, intracellular dopamine concentration were decreased and cell viability was changed in stable transfected G2019S cell lines. Dysregulation of dopamine metabolism, abnormal movement behavior and significant DA neuronal loss and locomotor deficits were found in the Drosophila G2019S mutants. Conclusion: LRRK2-G2019S variant is associated to PD. Dysregulation of dopamine metabolism caused by LRRK2-G2019S could modulate the neuronal biochemical environment to enhance PD pathogenesis. |
| first_indexed | 2024-10-01T05:48:31Z |
| format | Final Year Project (FYP) |
| id | ntu-10356/65657 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T05:48:31Z |
| publishDate | 2015 |
| record_format | dspace |
| spelling | ntu-10356/656572023-02-28T18:06:14Z The study of dopamine metabolism with LRRK2 variants in Parkinson’s disease Kwok, Wei Hao Zhao Yi School of Biological Sciences Department of Clinical Research, Singapore General Hospital DRNTU::Science::Biological sciences::Human anatomy and physiology::Neurobiology Background: Parkinson's disease (PD) is a neurodegenerative disease in which symptoms typically appear when a loss of dopaminergic (DA) neurons causes dopamine levels to fall significantly. Leucine rich repeat kinase 2 (LRRK2) gene mutations are the most common genetic cause of PD. Dopamine decarboxylase (DDC) and dopamine beta hydroxylase (DBH) are critical enzymes involved in dopamine metabolism. Previous gene expression profiling have revealed that DDC and DBH were downregulated in LRRK2-G2019S variant stable transfected cell lines in comparison with wild type LRRK2. Approach: In this study, the dopamine metabolism in stable transfected SH-SY5Y cell lines and Drosophila models were investigated. Real-time polymerase chain reaction (PCR), high performance liquid chromatography (HPLC) and cell morphology test were used for the study. Results: The results confirmed that DDC and DBH were downregulated, intracellular dopamine concentration were decreased and cell viability was changed in stable transfected G2019S cell lines. Dysregulation of dopamine metabolism, abnormal movement behavior and significant DA neuronal loss and locomotor deficits were found in the Drosophila G2019S mutants. Conclusion: LRRK2-G2019S variant is associated to PD. Dysregulation of dopamine metabolism caused by LRRK2-G2019S could modulate the neuronal biochemical environment to enhance PD pathogenesis. Bachelor of Science in Biomedical Sciences 2015-12-01T08:42:58Z 2015-12-01T08:42:58Z 2015 2015 Final Year Project (FYP) http://hdl.handle.net/10356/65657 en Nanyang Technological University 29 p. application/pdf |
| spellingShingle | DRNTU::Science::Biological sciences::Human anatomy and physiology::Neurobiology Kwok, Wei Hao The study of dopamine metabolism with LRRK2 variants in Parkinson’s disease |
| title | The study of dopamine metabolism with LRRK2 variants in Parkinson’s disease |
| title_full | The study of dopamine metabolism with LRRK2 variants in Parkinson’s disease |
| title_fullStr | The study of dopamine metabolism with LRRK2 variants in Parkinson’s disease |
| title_full_unstemmed | The study of dopamine metabolism with LRRK2 variants in Parkinson’s disease |
| title_short | The study of dopamine metabolism with LRRK2 variants in Parkinson’s disease |
| title_sort | study of dopamine metabolism with lrrk2 variants in parkinson s disease |
| topic | DRNTU::Science::Biological sciences::Human anatomy and physiology::Neurobiology |
| url | http://hdl.handle.net/10356/65657 |
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