The study of dopamine metabolism with LRRK2 variants in Parkinson’s disease

• Main Author: Kwok, Wei Hao
• Other Authors: Zhao Yi
• Format: Final Year Project
• Language: English
• Published: 2015
• Subjects: DRNTU::Science::Biological sciences::Human anatomy and physiology::Neurobiology
• Online Access: http://hdl.handle.net/10356/65657
• Institution: Nanyang Technological University

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.