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dc.contributor.authorChia, Xin Tian
dc.description.abstractBackground: LRRK2 mutations are the most common genetic cause of Parkinson’s disease (PD). Previously, a compelling link between dopamine metabolic dysregulation and PD pathogenesis has been established. Specifically, dopamine synthesis enzymes were reportedly down-regulated in LRRK2 mutants G2019S and G2385R. Approach: Herein, the dysregulation of dopamine metabolism was further characterized in the dopamine degradation pathway of LRRK2 mutants. Protein expression of degradative enzymes (COMT and MAO) was determined using western immunoblot. Intracellular dopamine level was analysed using HPLC, while intracellular ROS and neuronal viability were monitored using cellular assays. Results: No significant changes were found in COMT and MAO-B protein levels between WT and LRRK2 mutants. Whereas, reduced dopamine levels in LRRK2 variants could indicate that dopamine homeostasis is impaired. ROS and neurotoxicity were evidently increased in LRRK2 mutants, and further enhanced under oxidative stress. Conclusion: Together with previous studies, the findings support the dysregulation of dopamine metabolism in LRRK2 mutants, as degradative enzymes were disproportional to the down-regulated synthesis enzymes. Enhanced neurotoxicity in LRRK2 mutants contends that dysregulated dopamine metabolism might underlie PD vulnerability, by increasing ROS generation, and thus potentiating neurotoxicity. Hence, the dysregulation of dopamine metabolism could modulate the neuronal biochemical environment to enhance PD pathogenesis.en_US
dc.format.extent29 p.en_US
dc.rightsNanyang Technological University
dc.subjectDRNTU::Science::Biological sciences::Biochemistryen_US
dc.titleDysregulated dopamine metabolism in LRRK2 mutantsen_US
dc.typeFinal Year Project (FYP)en_US
dc.contributor.supervisorZhao Yien_US
dc.contributor.schoolSchool of Biological Sciencesen_US
dc.description.degreeBachelor of Science in Biological Sciencesen_US
dc.contributor.organizationSingapore General Hospital, Department of Clinical Researchen_US
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Appears in Collections:SBS Student Reports (FYP/IA/PA/PI)
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