Small Molecules and Peptides Targeting Glial Cell Line-Derived Neurotrophic Factor Receptors for the Treatment of Neurodegeneration
Autor: | Mart Saarma, Yulia Sidorova |
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Rok vydání: | 2020 |
Předmět: |
Receptor complex
Neurturin Review Ligands lcsh:Chemistry chemistry.chemical_compound 0302 clinical medicine Drug Delivery Systems Neurotrophic factors Glial cell line-derived neurotrophic factor Receptor lcsh:QH301-705.5 Spectroscopy Cells Cultured Neurons 0303 health sciences biology Neurodegeneration neurodegeneration Neurodegenerative Diseases General Medicine 3. Good health Computer Science Applications Neuroglia Signal Transduction Cell type Glial Cell Line-Derived Neurotrophic Factor Receptors small molecule Receptors Nerve Growth Factor GFL mimetic Catalysis Inorganic Chemistry Small Molecule Libraries 03 medical and health sciences retinitis pigmentosa medicine Neurites Animals Humans Glial Cell Line-Derived Neurotrophic Factor Physical and Theoretical Chemistry Molecular Biology 030304 developmental biology Alpha-synuclein neuropathic pain Organic Chemistry medicine.disease RET agonist lcsh:Biology (General) lcsh:QD1-999 chemistry biology.protein Parkinson’s disease Neuralgia glial cell line-derived neurotrophic factor (GDNF) family ligands (GFLs) receptor tyrosine kinase Rearranged in Transfection (RET) Peptides Neuroscience 030217 neurology & neurosurgery |
Zdroj: | International Journal of Molecular Sciences International Journal of Molecular Sciences, Vol 21, Iss 6575, p 6575 (2020) |
ISSN: | 1422-0067 |
Popis: | Glial cell line-derived neurotrophic factor (GDNF) family ligands (GFLs) are able to promote the survival of multiple neuronal populations in the body and, therefore, hold considerable promise for disease-modifying treatments of diseases and conditions caused by neurodegeneration. Available data reveal the potential of GFLs for the therapy of Parkinson’s disease, neuropathic pain and diseases caused by retinal degeneration but, also, amyotrophic lateral sclerosis and, possibly, Alzheimer’s disease. Despite promising data collected in preclinical models, clinical translation of GFLs is yet to be conducted. The main reasons for the limited success of GFLs clinical development are the poor pharmacological characteristics of GFL proteins, such as the inability of GFLs to cross tissue barriers, poor diffusion in tissues, biphasic dose-response and activation of several receptors in the organism in different cell types, along with ethical limitations on patients’ selection in clinical trials. The development of small molecules selectively targeting particular GFL receptors with improved pharmacokinetic properties can overcome many of the difficulties and limitations associated with the clinical use of GFL proteins. The current review lists several strategies to target the GFL receptor complex with drug-like molecules, discusses their advantages, provides an overview of available chemical scaffolds and peptides able to activate GFL receptors and describes the effects of these molecules in cultured cells and animal models. |
Databáze: | OpenAIRE |
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