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

Oh SM, Chang MY, Song JJ, Rhee YH, Joe EH, Lee HS, Yi SH, Lee SH - EMBO Mol Med (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, Hanyang University, Seoul, Korea Hanyang Biomedical Research Institute, Hanyang University, Seoul, Korea Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, Korea.

No MeSH data available.


Related in: MedlinePlus

Schematic representation of mDA neuron survival promoted by forced Nurr1 + Foxa2 gene deliveryNurr1 and Foxa2 are endogenously expressed in mDA neurons and promote cell survival in a cell-autonomous manner (left). Expression of Nurr1 and Foxa2 is reduced in mDA neurons during aging and degenerative processes. In addition, glia come to be polarized toward the harmful M1-type. DA neurons with reduced Nurr1/Foxa2 expression are more vulnerable to the toxic environment in the aged or degenerating midbrain (middle). Forced expression of Nurr1 + Foxa2 in mDA neurons promotes their survival. In addition, Nurr1 + Foxa2 transgene expression in glial cells (M2-type) creates a neuroprotective environment by suppressing the secretion of pro-inflammatory cytokines as well as promoting neurotrophic factor release (right).
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fig06: Schematic representation of mDA neuron survival promoted by forced Nurr1 + Foxa2 gene deliveryNurr1 and Foxa2 are endogenously expressed in mDA neurons and promote cell survival in a cell-autonomous manner (left). Expression of Nurr1 and Foxa2 is reduced in mDA neurons during aging and degenerative processes. In addition, glia come to be polarized toward the harmful M1-type. DA neurons with reduced Nurr1/Foxa2 expression are more vulnerable to the toxic environment in the aged or degenerating midbrain (middle). Forced expression of Nurr1 + Foxa2 in mDA neurons promotes their survival. In addition, Nurr1 + Foxa2 transgene expression in glial cells (M2-type) creates a neuroprotective environment by suppressing the secretion of pro-inflammatory cytokines as well as promoting neurotrophic factor release (right).


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

Oh SM, Chang MY, Song JJ, Rhee YH, Joe EH, Lee HS, Yi SH, Lee SH - EMBO Mol Med (2015)

Schematic representation of mDA neuron survival promoted by forced Nurr1 + Foxa2 gene deliveryNurr1 and Foxa2 are endogenously expressed in mDA neurons and promote cell survival in a cell-autonomous manner (left). Expression of Nurr1 and Foxa2 is reduced in mDA neurons during aging and degenerative processes. In addition, glia come to be polarized toward the harmful M1-type. DA neurons with reduced Nurr1/Foxa2 expression are more vulnerable to the toxic environment in the aged or degenerating midbrain (middle). Forced expression of Nurr1 + Foxa2 in mDA neurons promotes their survival. In addition, Nurr1 + Foxa2 transgene expression in glial cells (M2-type) creates a neuroprotective environment by suppressing the secretion of pro-inflammatory cytokines as well as promoting neurotrophic factor release (right).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4492814&req=5

fig06: Schematic representation of mDA neuron survival promoted by forced Nurr1 + Foxa2 gene deliveryNurr1 and Foxa2 are endogenously expressed in mDA neurons and promote cell survival in a cell-autonomous manner (left). Expression of Nurr1 and Foxa2 is reduced in mDA neurons during aging and degenerative processes. In addition, glia come to be polarized toward the harmful M1-type. DA neurons with reduced Nurr1/Foxa2 expression are more vulnerable to the toxic environment in the aged or degenerating midbrain (middle). Forced expression of Nurr1 + Foxa2 in mDA neurons promotes their survival. In addition, Nurr1 + Foxa2 transgene expression in glial cells (M2-type) creates a neuroprotective environment by suppressing the secretion of pro-inflammatory cytokines as well as promoting neurotrophic factor release (right).
Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, Hanyang University, Seoul, Korea Hanyang Biomedical Research Institute, Hanyang University, Seoul, Korea Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, Korea.

No MeSH data available.


Related in: MedlinePlus