This title appears in the Scientific Report :
2019
Please use the identifier:
http://hdl.handle.net/2128/23845 in citations.
Please use the identifier: http://dx.doi.org/10.4236/wjns.2019.94022 in citations.
Small-Molecule Ligands as Challenge for Positron Emission Tomography of Peptide Receptors in Neurons and Microglia of the Brain
Small-Molecule Ligands as Challenge for Positron Emission Tomography of Peptide Receptors in Neurons and Microglia of the Brain
Neuropeptide and chemokine receptors of the G protein-coupled receptor(GPCR) family belong to different classes and subgroups providing differentdocking sites and special binding behavior at extracellular and also transmembranedomains for small molecules potentially suitable for positronemission tom...
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Personal Name(s): | Pissarek, Margit (Corresponding author) |
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Contributing Institute: |
Nuklearchemie; INM-5 |
Published in: | World Journal of Neuroscience, 09 (2019) 04, S. 294 - 327 |
Imprint: |
Irvine, CA
Scientific Research Publ.
2019
|
DOI: |
10.4236/wjns.2019.94022 |
Document Type: |
Journal Article |
Research Program: |
Neuroimaging |
Subject (ZB): | |
Link: |
OpenAccess OpenAccess |
Publikationsportal JuSER |
Please use the identifier: http://dx.doi.org/10.4236/wjns.2019.94022 in citations.
Neuropeptide and chemokine receptors of the G protein-coupled receptor(GPCR) family belong to different classes and subgroups providing differentdocking sites and special binding behavior at extracellular and also transmembranedomains for small molecules potentially suitable for positronemission tomography (PET). The contribution gives an overview updatingdevelopments of small-molecule, nonpeptide ligands at a selection of peptideand chemokine receptors, expressed in neurons and microglia of the brain,regarding the last five years. Orexin 1 and orexin 2 receptors (OX1R; OX2R)and neuropeptide Y1 and Y2 receptors (NPY1R, NPY2R) were chosen asrepresentatives of Class A neuropeptide receptors, chemokine receptor CX3C(CX3CR1) as Class A, protein-activated receptor, highly expressed in activatedmicroglia, and corticotropin releasing factor receptor 1 (CRFR1) asrepresentative Class B1 receptor. Structural differences between binding domainsand their endogenous ligands as well as parallel expression in differenttypes of cells and generally low density of these receptors in brain tissue arefactors making the search for selective and sensitive ligands more difficultthan for classical GPCR receptors. Main progress in ligand development isobserved for NPY receptor antagonists and orexin receptor antagonists. Fororexin receptors, search for suitable ligands can be supported with modellingapproaches, as recently the complete molecular structure of these receptors isavailable. Small molecules, binding at CRFR1, as for other Class B1 receptorligands, in PET and investigations of pharmacodynamics revealed rather allostericbinding modes, although, the complete crystal structure of CRFR1 asprototype of Class B1 provides, hitherto, improved possibilities for understandingbinding mechanisms. Highly specific as a marker of microglia amongthe GPCRs, CX3CR1 is focused as target of PET during inflammation ofbrain and spinal cord. |