Glial cell line-derived neurotrophic factors (GFLs) and small molecules targeting RET receptor for the treatment of pain and Parkinson's disease
| Autor: | Mahato, Arun Kumar, Sidorova, Yulia A. |
|---|---|
| Přispěvatelé: | Institute of Biotechnology |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Glial cell line-neurotrophic factor (GDNF)
artemin (ARTN) GDNF-FAMILY NEUROPATHIC PAIN RET receptor tyrosine kinase Drug development DOPAMINERGIC-NEURONS Drug design GDNF family ligands (GFLs) RET agonist DOUBLE-BLIND BEHAVIORAL SENSITIVITY MEDIATED GENE-TRANSFER NEURONS IN-VITRO RAT MODEL RET receptor SENSORY NEURONS 1182 Biochemistry cell and molecular biology SPINAL NERVE LIGATION Small molecule Neurturin (NRTN) |
| Popis: | Rearranged during transfection (RET), in complex with glial cell line-derived (GDNF) family receptor alpha (GFR alpha), 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 GFR alpha 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. |
| Databáze: | OpenAIRE |
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