The polysialic acid mimetics 5-nonyloxytryptamine and vinorelbine facilitate nervous system repair.
Polysialic acid (PSA) is a large negatively charged glycan mainly attached to the neural cell adhesion molecule (NCAM). Several studies have shown that it is important for correct formation of brain circuitries during development and for synaptic plasticity, learning and memory in the adult. PSA also plays a major role in nervous system regeneration following injury. As a next step for clinical translation of PSA based therapeutics, we have previously identified the small organic compounds 5-nonyloxytryptamine and vinorelbine as PSA mimetics. Activity of 5-nonyloxytryptamine and vinorelbine had been confirmed in assays with neural cells from the central and peripheral nervous system in vitro and shown to be independent of their function as serotonin receptor 5-HT1B/1D agonist or cytostatic drug, respectively. As we show here in an in vivo paradigm for spinal cord injury in mice, 5-nonyloxytryptamine and vinorelbine enhance regain of motor functions, axonal regrowth, motor neuron survival and remyelination. These data indicate that 5-nonyloxytryptamine and vinorelbine may be re-tasked from their current usage as a 5-HT1B/1D agonist or cytostatic drug to act as mimetics for PSA to stimulate regeneration after injury in the mammalian nervous system.
Department of Biotechnology, Guru Nanak Dev University, GT Road, 143005 Amritsar, India.|Center for Molecular Neurobiology, University Hospital Hamburg-Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany.
Vedangana
V
Saini
Center for Molecular Neurobiology, University Hospital Hamburg-Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany.
David
D
Lutz
Center for Molecular Neurobiology, University Hospital Hamburg-Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany.
Hardeep
H
Kataria
Department of Biotechnology, Guru Nanak Dev University, GT Road, 143005 Amritsar, India.
Gurcharan
G
Kaur
Keck Center for Collaborative Neurosciences, Rutgers University, Piscataway, NJ 08854, USA.|Center for Neuroscience, Shantou University Medical College, Shantou, Guangdong 515041, People's Republic of China.
Melitta
M
Schachner
Center for Molecular Neurobiology, University Hospital Hamburg-Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany.
Gabriele
G
Loers
D000818:Animals; D054697:Cytostatic Agents / Q000008:administration & dosage; D051379:Mice; D009046:Motor Neurons / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D009416:Nerve Regeneration / Q000187:drug effects*; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism; D009473:Neuronal Plasticity / Q000187:drug effects; D058825:Serotonin 5-HT1 Receptor Agonists / Q000008:administration & dosage; D012794:Sialic Acids / Q000008:administration & dosage / Q000737:chemistry; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology; D014363:Tryptamines / Q000008:administration & dosage / Q000737:chemistry; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine; D014945:Wound Healing / Q000187:drug effects*
D054697:Cytostatic Agents; D019006:Neural Cell Adhesion Molecules; D058825:Serotonin 5-HT1 Receptor Agonists; D012794:Sialic Acids; D014363:Tryptamines; C021319:polysialic acid; C030820:tryptamine; D014747:Vinblastine; D000077235:Vinorelbine