Combined Nurr1 and Foxa2 roles in the therapy of Parkinson's disease

Title
Combined Nurr1 and Foxa2 roles in the therapy of Parkinson's disease
Authors
이상훈
Keywords
Foxa2; gene therapy; midbrain dopamine neuron; Nurr1; Parkinson's disease
Issue Date
2015-05
Publisher
WILEY-BLACKWELL
Citation
EMBO MOLECULAR MEDICINE, v. 7, NO 5, Page. 510-525
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 bimodal 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 1year, suggesting that expression of these factors is a promising approach in PD therapy.
URI
http://embomolmed.embopress.org/content/7/5/510http://hdl.handle.net/20.500.11754/24748
ISSN
1757-4676; 1757-4684
DOI
http://dx.doi.org/10.15252/emmm.201404610
Appears in Collections:
COLLEGE OF MEDICINE[S](의과대학) > MEDICINE(의학과) > Articles
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