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Pharmacological Properties and Biological Functions of the GPR17 Receptor, a Potential Target for Neuro-Regenerative Medicine

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Protein Reviews

Part of the book series: Advances in Experimental Medicine and Biology ((PROTRE,volume 1051))

Abstract

In 2006, cells heterologously expressing the “orphan” receptor GPR17 were shown to acquire responses to both uracil nucleotides and cysteinyl-leukotrienes, two families of signaling molecules accumulating in brain or heart as a result of hypoxic/traumatic injuries. In subsequent years, evidence of GPR17 key role in oligodendrogenesis and myelination has highlighted it as a “model receptor” for new therapies in demyelinating and neurodegenerative diseases. The apparently contrasting evidence in the literature about the role of GPR17 in promoting or inhibiting myelination can be due to its transient expression in the intermediate stages of differentiation, exerting a pro-differentiating function in early oligodendrocyte precursor cells (OPCs), and an inhibitory role in late stage maturing cells. Meanwhile, several papers extended the initial data on GPR17 pharmacology, highlighting a “promiscuous” behavior of this receptor; indeed, GPR17 is able to respond to other emergency signals like oxysterols or the pro-inflammatory cytokine SDF-1, underlying GPR17 ability to adapt its responses to changes of the surrounding extracellular milieu, including damage conditions. Here, we analyze the available literature on GPR17, in an attempt to summarize its emerging biological roles and pharmacological properties.

Marta Fumagalli and Davide Lecca contributed equally to this work.

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Abbreviations

CNS:

central nervous system

cysLT:

cysteinyl-leukotrienes

EAE:

experimental autoimmune encephalomyelitis

ERK1/2:

extracellular signal–regulated kinases 1 and 2

FACS-MS:

frontal affinity chromatography-mass spectrometry

GPCRs:

G-protein coupled receptors

HM:

homology modeling

Lys:

lysolecithin

MCAo:

middle cerebral artery occlusion

MS:

multiple sclerosis

NC-IUPHAR:

Nomenclature Committee of the International Union of Pharmacology

OLs:

oligodendrocytes

OPCs:

oligodendrocyte precursor cells

MBP:

myelin basic protein

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Acknowledgements

Authors are deeply grateful to the Italian Multiple Sclerosis (FISM) for financial support (Projects N. 2013/R1 to MPA) and to Cariplo Foundation (Projects 2014-1207 to DL and 2015-0910 to MF).

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The authors declare no conflicts of interest.

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    Authors and Affiliations

    1. Laboratory of Molecular and Cellular Pharmacology of Purinergic Transmission, Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Via Balzaretti 9, 20133, Milan, Italy

      Marta Fumagalli, Davide Lecca, Giusy T. Coppolino, Chiara Parravicini & Maria P. Abbracchio

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    1. Marta Fumagalli
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    2. Davide Lecca
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    3. Giusy T. Coppolino
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    4. Chiara Parravicini
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    5. Maria P. Abbracchio
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    Correspondence to Maria P. Abbracchio .

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    1. Biochem and Mol Biol, Baylor College of Medicine, Houston, Texas, USA

      M. Zouhair Atassi

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    Fumagalli, M., Lecca, D., Coppolino, G.T., Parravicini, C., Abbracchio, M.P. (2017). Pharmacological Properties and Biological Functions of the GPR17 Receptor, a Potential Target for Neuro-Regenerative Medicine. In: Atassi, M. (eds) Protein Reviews. Advances in Experimental Medicine and Biology(), vol 1051. Springer, Singapore. https://doi.org/10.1007/5584_2017_92

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