Leucine-rich repeat kinase 2 (LRRK2) and tau regulate synaptic function and neuronal anti-oxidant mechanism

• Main Authors: Huang, Yi Chun, 黃伊駿
• Other Authors: Chang, Hui Yun
• Format: Others
• Language: en_US
• Published: 2017
• Online Access: http://ndltd.ncl.edu.tw/handle/ctwt3h

碩士 === 國立清華大學 === 系統神經科學研究所 === 105 === LRRK2 is a multi-functional protein regulating many mechanisms. Many studies have reported that LRRK2 mutation with higher kinase activity is highly related to Parkinson’s disease. Expression of tau causes tau protein aggregate in the cytosol, which leads to neuron death in many neurodegenerative diseases. Recently, many studies show that not only neurons but synaptic function is affected in the patient’s brain. In this study, we use Drosophila as a model to investigate how LRRK2 and tau affect neurotransmission on the different types of neurons in the brain. We find that overexpression of Tau in the dopaminergic system disrupted neurotransmission at the mushroom body but co-expression of LRRK2 can rescue this defect. However, expression of LRRK2G2019S exacerbated the deficit. Although expression of tau in the glutamatergic neurons caused a reduction of the neurotransmission at antenna mechanosensory and motor center, expression of LRRK2 does not rescue the neurotransmission. Moreover, LRRK2G2019S does not worsen the defect. Taken together, LRRK2 may have different effect in different neuron systems. Studies also indicated that higher oxidative stress occurs in neurodegenerative disease patient’s brain and oxidative stress may induce neuron death in the brain. Antioxidant proteins are important to deal with oxidative stress. It is known that Nrf2 can bind to ARE and activate downstream antioxidant proteins synthesis. In present study, we find that overexpression of tau in the dopaminergic or the glutamatergic neurons could reduce Nrf2 level in the brain but expression of LRRK2 can rescue the defect. In addition, expression of LRRK2G2019S in the dopaminergic neurons aggravates defect. In summary, our study shows LRRK2 and tau have functional interaction in many aspects.