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Expression of Human LRRK2 affects lifespan, ATP and oxidative stress in animal model of Drosophila.
Thesis

Expression of Human LRRK2 affects lifespan, ATP and oxidative stress in animal model of Drosophila.

Hsiao, Ping-Yen
Masters, 國立清華大學, 系統神經科學研究所
2012

Abstract

LRRK2蛋白 三磷酸腺苷 氧化壓力 壽命 LRRK2 ATP Oxidative stress Life-span
Parkinson’s disease is one of the common neuron degeneration diseases. The obvious symptom was shacking and movement dysfunction that is caused by degeneration dopamine neuron in substantia nigra. Leucine-rich repeat kinase 2 (LRRK2) is an important gene association with Parkinson’s disease. Mutation in LRRK2, the most common known cause of autosomal dominant PD, is also found in ‘sporadic’ cases. PD patient’s brain tissue with LRRK2 mutations has accumulation of a-synuclein and/or tau protein aggregates. Many previous studies focus on mutation LRRK2; however, normal LRRK2 function remains unclear. Therefore, we investigated the role of LRRK2 through GAL4/UAS system, in Drosophila. In our studies, we found LRRK2 expression in fly brains or DA neurons can decrease Drosophila mortality. Furthermore, we found that LRRK2 expression can partially rescue apoptotic cell death induced by Grim, or Hid. Finally, we showed that LRRK2 expression in neurons can increase ATP levels and oxidative stress. Taken together, our results suggest that LRRK2 function is critical for neuronal survival which might be useful to realize how LRRK2 mutation mediates Parkinson’s disease due to (LOF) loss of function, and may help for future therapeutic intervention.

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