Combined Nurr1 and Foxa2 roles in the therapy of Parkinson's disease
| Autor: | Jae Jin Song, Sang Min Oh, Sang Hoon Yi, Yong Hee Rhee, Sang-Hun Lee, Eun Hye Joe, Hyun Seob Lee, Mi Yoon Chang |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Male
0301 basic medicine Parkinson's disease Genetic enhancement Biology Neurotransmission Gene delivery Foxa2 Bioinformatics Midbrain 03 medical and health sciences Paracrine signalling 0302 clinical medicine Mesencephalon Nuclear Receptor Subfamily 4 Group A Member 2 medicine Animals Transcription factor Cells Cultured Research Articles Mice Inbred ICR business.industry Dopaminergic Neurons Parkinson Disease Genetic Therapy medicine.disease gene therapy Disease Models Animal Nurr1 Treatment Outcome 030104 developmental biology nervous system Hepatocyte Nuclear Factor 3-beta Cancer research Molecular Medicine midbrain dopamine neuron FOXA2 Corrigendum business Neuroglia Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | EMBO Molecular Medicine |
| ISSN: | 1757-4684 1757-4676 |
| Popis: | 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 1 year, suggesting that expression of these factors is a promising approach in PD therapy. |
| Databáze: | OpenAIRE |
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