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Driving GDNF expression: The green and the red traffic lights
- Source :
- Repositório Científico de Acesso Aberto de Portugal, Repositório Científico de Acesso Aberto de Portugal (RCAAP), instacron:RCAAP
- Publication Year :
- 2008
- Publisher :
- Elsevier BV, 2008.
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- ISSN :
- 03010082
- Volume :
- 86
- Database :
- OpenAIRE
- Journal :
- Progress in Neurobiology
- Accession number :
- edsair.doi.dedup.....483d4e0d5de74a29abc2b6fea2fa0ea1