ORCID
- James A. Conway: 0000-0002-6044-4602
- Edgar R. Kramer: 0000-0002-4882-4143
Abstract
The neurotrophic signaling of glial cell line-derived neurotrophic factor (GDNF) with its canonical receptor, the receptor tyrosine kinase RET, coupled together with the GDNF family receptor alpha 1 is important for dopaminergic neuron survival and physiology in cell culture experiments and animal models. This prompted the idea to try GDNF/RET signaling as a therapeutic approach to treat Parkinson's disease with the hallmark of dopaminergic cell death in the substantia nigra of the midbrain. Despite several clinical trials with GDNF in Parkinson's disease patients, which mainly focused on optimizing the GDNF delivery technique, benefits were only seen in a few patients. In general, the endpoints did not show significant improvements. This suggests that it will be helpful to learn more about the basic biology of this fascinating but complicated GDNF/RET signaling system in the dopaminergic midbrain and about recent developments in the field to facilitate its use in the clinic. Here we will refer to the latest publications and point out important open questions in the field.
DOI
10.4103/1673-5374.327330
Publication Date
2021-12-10
Publication Title
Neural Regeneration Research
Volume
17
Issue
7
ISSN
1673-5374
Keywords
Clinical trials, Dopaminergic neurons, GFRα1, Glial cell line-derived neurotrophic factor, Gut-brain axis, Nedd4, Parkin, Parkinson's disease, RET, α-synuclein
First Page
1462
Last Page
1467
Recommended Citation
Kramer, E., & Conway, J. (2021) 'Is activation of GDNF/RET signaling the answer for successful treatment of Parkinson's disease? A discussion of data from the culture dish to the clinic', Neural Regeneration Research, 17(7), pp. 1462-1467. Available at: https://doi.org/10.4103/1673-5374.327330
