Dysregulation of dopamine metabolism in LRRK2-associated Parkinson's disease.

• Main Author: Chan, Clarice Zi Ying.
• Other Authors: Surajit Bhattacharyya
• Format: Final Year Project
• Language: English
• Published: 2013
• Subjects: DRNTU::Science
• Online Access: http://hdl.handle.net/10356/52902
• Institution: Nanyang Technological University

Background: Parkinson’s disease (PD) is a common, age-related, progressive and debilitating neurodegenerative disorder. Mutations in Leucine Rich Repeat Kinase 2 gene (LRRK2) are the cause of familial and sporadic PD. The pathophysiological role of LRRK2 in PD remains unclear. Our preliminary data showed that gene expression profiling were significantly different in wild type, G2019S and G2385R - LRRK2 stable transfected SH-SY5Y cell lines. Dopamine beta-hydroxylase (DBH) and DOPA decarboxylase (DDC) genes, found to be down regulated in the gene expression profiling, were verified by Real-time PCR. Dysregulation of dopamine metabolism is an important pathogenesis relevant to PD. In this project, we aim to identify the down regulations of DDC and DBH using LRRK2 stable transfected cell and transgenic drosophila model. Methodology/Principal findings: Western blotting has confirmed that there are significant down regulations of DDC and DBH in G2019S variant cells under normal and oxidative stress conditions. In G2385R variant cells, DBH expression levels were found to be significantly lower under both conditions as compared to wild type stable cells. This finding has verified previous gene expression profiling. Conclusion/Significance: Our results show that LRRK2 gene mutations play a critical role in the pathogenesis of PD by the dysregulation of dopamine metabolism as seen in LRRK2 variants stable transfection cell lines.