AI Article Synopsis
- RET is the main receptor for glial cell line-derived neurotrophic factors (GFLs), important for the health and survival of dopamine and sensory neurons.
- Research shows promising effects of GFLs in animal models for treating Parkinson's disease and neuropathic pain, but clinical trials have been inconclusive due to their poor drug-like properties.
- Developing small molecule drugs that target RET and/or GFRα could offer a new approach for treating these diseases more effectively.
Article Abstract
Rearranged during transfection (RET), in complex with glial cell line-derived (GDNF) family receptor alpha (GFRα), is the canonical signaling receptor for GDNF family ligands (GFLs) expressed in both central and peripheral parts of the nervous system and also in non-neuronal tissues. RET-dependent signaling elicited by GFLs has an important role in the development, maintenance and survival of dopamine and sensory neurons. Both Parkinson's disease and neuropathic pain are devastating disorders without an available cure, and at the moment are only treated symptomatically. GFLs have been studied extensively in animal models of Parkinson's disease and neuropathic pain with remarkable outcomes. However, clinical trials with recombinant or viral vector-encoded GFL proteins have produced inconclusive results. GFL proteins are not drug-like; they have poor pharmacokinetic properties and activate multiple receptors. Targeting RET and/or GFRα with small molecules may resolve the problems associated with using GFLs as drugs and can result in the development of therapeutics for disease-modifying treatments against Parkinson's disease and neuropathic pain.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7529621 | PMC |
| http://dx.doi.org/10.1007/s00441-020-03227-4 | DOI Listing |
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