Remyelination, namely, the formation of new myelin sheaths around denuded axons, counteracts axonal degeneration and restores neuronal function. Considerable advances have been made in understanding this regenerative process that often fails in diseases like multiple sclerosis, leaving axons demyelinated and vulnerable to damage, thus contributing to disease progression. The identification of the membrane receptor GPR17 on a subset of oligodendrocyte precursor cells (OPCs), which mediate remyelination in the adult central nervous system (CNS), has led to a huge amount of evidence that validated this receptor as a new attractive target for remyelinating therapies. Here, we summarize the role of GPR17 in OPC function, myelination and remyelination, describing its atypical pharmacology, its downstream signaling, and the genetic and epigenetic factors modulating its activity. We also highlight crucial insights into GPR17 pathophysiology coming from the demonstration that oligodendrocyte injury, associated with inflammation in chronic neurodegenerative conditions, is invariably characterized by abnormal and persistent GPR17 upregulation, which, in turn, is accompanied by a block of OPCs at immature premyelinating stages. Finally, we discuss the current literature in light of the potential exploitment of GPR17 as a therapeutic target to promote remyelination.
Regulation and signaling of the GPR17 receptor in oligodendroglial cells / D. Lecca, S. Raffaele, M.P. Abbracchio, M. Fumagalli. - In: GLIA. - ISSN 0894-1491. - 68:10(2020 Oct), pp. 1957-1967.
|Titolo:||Regulation and signaling of the GPR17 receptor in oligodendroglial cells|
LECCA, DAVIDE (Primo)
RAFFAELE, STEFANO (Secondo)
ABBRACCHIO, MARIA PIA (Penultimo) (Corresponding)
FUMAGALLI, MARTA (Ultimo)
|Parole Chiave:||GPR17; neuroinflammatory diseases; oligodendrocyte progenitors; remyelination; signal transduction|
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
|Progetto:||Effects of microglia-derived vesicles on GPR17-expressing oligodendrocyte precursors and remyelination after brain ischemia: new molecular insights and recovery potential|
New strategies to enhance the trophic functions and rem yelinating abilities of adult NG2-glia in am yotrophic lateral sclerosis via the GPR17 receptor
New strategies to enhance the trophic functions and remyelinating abilities of adult NG2-glia in amyotrophic lateral sclerosis via the GPR17 receptor (GPR17ALS-1)
Dipartimenti di Eccellenza 2018-2022 - Dipartimento di SCIENZE FARMACOLOGICHE E BIOMOLECOLARI
PIANO DI SOSTEGNO ALLA RICERCA 2015-2017 - LINEA 2 "DOTAZIONE ANNUALE PER ATTIVITA' ISTITUZIONALE"
|Data di pubblicazione:||ott-2020|
|Data ahead of print / Data di stampa:||22-feb-2020|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1002/glia.23807|
|Appare nelle tipologie:||01 - Articolo su periodico|