Transcriptional Regulation of Alpha-synuclein by GATA2 in Substantia Nigra

摘要: Parkinson’s disease (PD) is a chronic, progressive movement disorder that affects millions of patients and their families worldwide. Treatment options address some the symptoms but do not affect progression disease. Central to motor PD are due, in part, slow, loss dopaminergic neurons substantia nigra pars compacta (SNc) consequent depletion neurotransmission striatum. As these cells die, they accumulate toxic levels various substances, such as aggregation-prone protein alpha-synuclein (a-syn, SNCA) iron. It known expression SNCA aberrantly high SNc brain, transcriptional mechanisms participate this dysregulation poorly understood. Recently, GATA2, transcription factor for its critical role hematopoiesis, was shown regulate positively directly vitro; however, it unknown whether mode regulation occurs vivo thereby relevant PD. In dissertation project, we assessed relevance GATA2 by testing two hypotheses mammalian model: 1) regulates neurons, 2) silencing confers protection against parkinsonian neurotoxin, rotenone. To test hypotheses, necessary first validate rat suitable model investigating function adult brain develop reagents vivo. Using viral-mediated gene approach, found rat. However, protective rotenone treatment Our findings significant provide demonstration SNCA, central importance pathogenesis. Although our data suggest useful therapeutic target PD, shed light on thus contributing understanding GATA biology brain.