title: Nonyloxytryptamine mimics polysialic acid and modulates neuronal and glial functions in cell culture.
abstract: Polysialic acid (PSA) is a major regulator of cell-cell interactions in the developing nervous system and in neural plasticity in the adult. As a polyanionic molecule with high water-binding capacity, PSA increases the intercellular space generating permissive conditions for cell motility. PSA enhances stem cell migration and axon path finding and promotes repair in the lesioned peripheral and central nervous systems, thus contributing to regeneration. As a next step in developing an improved PSA-based approach to treat nervous system injuries, we searched for small organic compounds that mimic PSA and identified as a PSA mimetic 5-nonyloxytryptamine oxalate, described as a selective 5-hydroxytryptamine receptor 1B (5-HT1B ) agonist. Similar to PSA, 5-nonyloxytryptamine binds to the PSA-specific monoclonal antibody 735, enhances neurite outgrowth of cultured primary neurons and process formation of Schwann cells, protects neurons from oxidative stress, reduces migration of astrocytes and enhances myelination in vitro. Furthermore, nonyloxytryptamine treatment enhances expression of the neural cell adhesion molecule (NCAM) and its polysialylated form PSA-NCAM and reduces expression of the microtubule-associated protein MAP2 in cultured neuroblastoma cells. These results demonstrate that 5-nonyloxytryptamine mimics PSA and triggers PSA-mediated functions, thus contributing to the repertoire of molecules with the potential to improve recovery in acute and chronic injuries of the mammalian peripheral and central nervous systems. Polysialic acid (PSA) plays important roles in nervous system development, as well as synaptic plasticity and regeneration in the adult. 5-Nonyloxytryptamine oxalate (5-NOT) mimics PSA and triggers PSA-mediated functions in neurons and glial cells. 5-NOT stimulates neuritogenesis, myelination and Schwann cell migration. This study sets the basis to develop a PSA-mediated therapy of acute and chronic nervous system diseases.
authors: Zentrum für Molekulare Neurobiologie Hamburg, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.
authors: Gabriele
authors: G
authors: Loers
authors: Vedangana
authors: V
authors: Saini
authors: Bibhudatta
authors: B
authors: Mishra
authors: Florentia
authors: F
authors: Papastefanaki
authors: David
authors: D
authors: Lutz
authors: Sidhartha
authors: S
authors: Chaudhury
authors: Daniel R
authors: DR
authors: Ripoll
authors: Anders
authors: A
authors: Wallqvist
authors: Sheraz
authors: S
authors: Gul
authors: Melitta
authors: M
authors: Schachner
authors: Gurcharan
authors: G
authors: Kaur
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009457:Neuroglia / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D017434:Protein Structure, Tertiary; D058825:Serotonin 5-HT1 Receptor Agonists / Q000737:chemistry / Q000494:pharmacology*; D012794:Sialic Acids / Q000737:chemistry / Q000494:pharmacology*; D014363:Tryptamines / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D058825:Serotonin 5-HT1 Receptor Agonists; D012794:Sialic Acids; D014363:Tryptamines; C021319:polysialic acid; C030820:tryptamine
keywords: 5-nonyloxytryptamine oxalate; migration; neural cell adhesion molecule; neurite outgrowth; polysialic acid; scratch injury