Premium
Nonyloxytryptamine mimics polysialic acid and modulates neuronal and glial functions in cell culture
Author(s) -
Loers Gabriele,
Saini Vedangana,
Mishra Bibhudatta,
Papastefanaki Florentia,
Lutz David,
Chaudhury Sidhartha,
Ripoll Daniel R.,
Wallqvist Anders,
Gul Sheraz,
Schachner Melitta,
Kaur Gurcharan
Publication year - 2014
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.12408
Subject(s) - polysialic acid , neural cell adhesion molecule , neurite , biology , microbiology and biotechnology , nervous system , neuroscience , axon , peripheral nervous system , central nervous system , neural stem cell , regeneration (biology) , stem cell , cell adhesion , cell , biochemistry , in vitro
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‐ HT 1B ) 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 MAP 2 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.