Receptors for myelin inhibitors: Structures and therapeutic opportunities.
Many studies have indicated that the inability of adult mammalian central nervous system (CNS) to regenerate after injury is partly due to the existence of growth-inhibitory molecules associated with CNS myelin. Studies over the years have led to the identification of multiple myelin-associated inhibitors, among which Nogo, myelin-associated glycoprotein (MAG) and oligodendrocyte-myelin glycoprotein (Omgp) represent potentially major contributors to CNS axon regeneration failure. Here we review in vitro and in vivo investigations into these inhibitory ligands and their functional mechanisms, focusing particularly on the neuronal receptors that mediate the inhibitory signals from these myelin molecules. A better understanding of the receptors for myelin-associated inhibitors could provide opportunities to decipher the mechanism of restriction in CNS regeneration, and lead to the development of potential therapeutic targets in neurodegenerative diseases and neurological injury. We will discuss the structures of the receptors and therapeutic opportunities that might arise based on this information.
Cao
Zixuan
Z
Neuroscience Discovery, Wyeth Research, Princeton, NJ 08543, USA.
Gao
Ying
Y
Deng
Kangwen
K
Williams
Gareth
G
Doherty
Patrick
P
Walsh
Frank S
FS
D000818:Animals; D001369:Axons / Q000502:physiology; D058851:GPI-Linked Proteins; D005732:Gangliosides / Q000737:chemistry / Q000378:metabolism; D006131:Growth Inhibitors / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D009185:Myelin Proteins / Q000378:metabolism*; D009186:Myelin Sheath / Q000378:metabolism*; D018992:Myelin-Associated Glycoprotein / Q000378:metabolism*; D063308:Myelin-Oligodendrocyte Glycoprotein; D009416:Nerve Regeneration / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000070798:Nogo Proteins; D011487:Protein Conformation; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000473:pathology
D058851:GPI-Linked Proteins; D005732:Gangliosides; D006131:Growth Inhibitors; C523678:LINGO1 protein, mouse; C571326:MOG protein, human; D008565:Membrane Proteins; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D009419:Nerve Tissue Proteins; D000070798:Nogo Proteins; C560528:OMG protein, human; C560529:Omg protein, mouse; C000603199:RTN4 protein, human; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; C000603201:Rtn4 protein, mouse