Coexpression of NURR1 and FOXA2 prevents midbrain dopamine neuron degeneration in Parkinson′s disease model
- Title
- Coexpression of NURR1 and FOXA2 prevents midbrain dopamine neuron degeneration in Parkinson′s disease model
- Author
- 오상민
- Advisor(s)
- 이상훈
- Issue Date
- 2016-02
- Publisher
- 한양대학교
- Degree
- Doctor
- Abstract
- Use of the physiological mechanisms promoting midbrain DA (mDA) neuron survival seems an appropriate option for developing treatments for Parkinson’s disease (PD). mDA neurons are specifically marked by expression of the transcription factors Nurr1 and Foxa2. We show herein that Nurr1 and Foxa2 interact to protect mDA neurons against various toxic insults, but their expression is lost during aging and degenerative processes. In addition to their proposed cell-autonomous actions in mDA neurons, forced expression of these factors in neighboring glia synergistically protects degenerating mDA neurons in a paracrine mode. As a consequence of these bi-modal actions, adeno-associated virus (AAV)-mediated gene delivery of Nurr1 and Foxa2 in a PD mouse model markedly protected mDA neurons and motor behaviors associated with nigrostriatal DA neurotransmission. The effects of the combined gene delivery were dramatic, highly reproducible and sustained for at least 1 year, suggesting that expression of these factors is a promising approach in PD therapy.
- URI
- https://repository.hanyang.ac.kr/handle/20.500.11754/126637http://hanyang.dcollection.net/common/orgView/200000427952
- Appears in Collections:
- GRADUATE SCHOOL OF BIOMEDICAL SCIENCE AND ENGINEERING[S](의생명공학전문대학원) > BIOMEDICAL SCIENCE(의생명과학과) > Theses (Ph.D.)
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