Small Molecules and Peptides Targeting Glial Cell Line-Derived Neurotrophic Factor Receptors for the Treatment of Neurodegeneration

Autor: Mart Saarma, Yulia Sidorova
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
Nepřihlášeným uživatelům se plný text nezobrazuje
načítá se...