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

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dc.contributor.author Sidorova, Yulia A.
dc.contributor.author Saarma, Mart
dc.date.accessioned 2020-11-24T10:28:12Z
dc.date.available 2020-11-24T10:28:12Z
dc.date.issued 2020-09
dc.identifier.citation Sidorova , Y A & Saarma , M 2020 , ' Small Molecules and Peptides Targeting Glial Cell Line-Derived Neurotrophic Factor Receptors for the Treatment of Neurodegeneration ' , International Journal of Molecular Sciences , vol. 21 , no. 18 , 6575 . https://doi.org/10.3390/ijms21186575
dc.identifier.other PURE: 151820914
dc.identifier.other PURE UUID: 14a9aae6-138b-41f1-97fb-c226ea0a53cb
dc.identifier.other WOS: 000579944000001
dc.identifier.other ORCID: /0000-0001-5543-7160/work/84259710
dc.identifier.uri http://hdl.handle.net/10138/321872
dc.description.abstract 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. en
dc.format.extent 20
dc.language.iso eng
dc.relation.ispartof International Journal of Molecular Sciences
dc.rights cc_by
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject glial cell line-derived neurotrophic factor (GDNF) family ligands (GFLs)
dc.subject receptor tyrosine kinase Rearranged in Transfection (RET)
dc.subject RET agonist
dc.subject GFL mimetic
dc.subject small molecule
dc.subject Parkinson's disease
dc.subject neuropathic pain
dc.subject neurodegeneration
dc.subject retinitis pigmentosa
dc.subject NEURONS-IN-VITRO
dc.subject GDNF FAMILY
dc.subject RAT MODEL
dc.subject ALPHA-SYNUCLEIN
dc.subject DOUBLE-BLIND
dc.subject PARKINSON DISEASE
dc.subject GENE DELIVERY
dc.subject WEIGHT-LOSS
dc.subject NEURTURIN
dc.subject SURVIVAL
dc.subject 1182 Biochemistry, cell and molecular biology
dc.title Small Molecules and Peptides Targeting Glial Cell Line-Derived Neurotrophic Factor Receptors for the Treatment of Neurodegeneration en
dc.type Review Article
dc.contributor.organization Divisions of Faculty of Pharmacy
dc.contributor.organization Institute of Biotechnology
dc.contributor.organization Helsinki Institute of Life Science HiLIFE, Joint Activities
dc.description.reviewstatus Peer reviewed
dc.relation.doi https://doi.org/10.3390/ijms21186575
dc.relation.issn 1422-0067
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

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