Driving GDNF expression: The green and the red traffic lights
| Autor: | Emília P. Duarte, Ana Saavedra, Graça Baltazar |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Parkinson's disease
animal diseases Gene Expression Nigrostriatal pathway Substantia nigra Development Models Biological Nervous System Neuroprotection Endogenous expression Activity dependence Signalling pathways Neuron-glia cross-talk Neurotrophic factors medicine Glial cell line-derived neurotrophic factor Animals Humans Glial Cell Line-Derived Neurotrophic Factor GDNF gene Inflammation biology urogenital system General Neuroscience Dopaminergic Neurodegeneration medicine.disease Nigrostriatal system medicine.anatomical_structure Gene Expression Regulation nervous system biology.protein Neuroscience GDNF family of ligands Signal Transduction |
| Zdroj: | Repositório Científico de Acesso Aberto de Portugal Repositório Científico de Acesso Aberto de Portugal (RCAAP) instacron:RCAAP |
| ISSN: | 0301-0082 |
| Popis: | Glial cell line-derived neurotrophic factor (GDNF) is widely recognized as a potent survival factor for dopaminergic neurons of the nigrostriatal pathway that degenerate in Parkinson's disease (PD). In animal models of PD, GDNF delivery to the striatum or the substantia nigra protects dopaminergic neurons against subsequent toxin-induced injury and rescues previously damaged neurons, promoting recovery of the motor function. Thus, GDNF was proposed as a potential therapy to PD aimed at slowing down, halting or reversing neurodegeneration, an issue addressed in previous reviews. However, the use of GDNF as a therapeutic agent for PD is hampered by the difficulty in delivering it to the brain. Another potential strategy is to stimulate the endogenous expression of GDNF, but in order to do that we need to understand how GDNF expression is regulated. The aim of this review is to do a comprehensive analysis of the state of the art on the control of endogenous GDNF expression in the nervous system, focusing mainly on the nigrostriatal pathway. We address the control of GDNF expression during development, in the adult brain and after injury, and how damaged neurons signal glial cells to up-regulate GDNF. Pharmacological agents or natural molecules that increase GDNF expression and show neuroprotective activity in animal models of PD are reviewed. We also provide an integrated overview of the signalling pathways linking receptors for these molecules to the induction of GDNF gene, which might also become targets for neuroprotective therapies in PD. |
| Databáze: | OpenAIRE |
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