4.4 Article

PSA mimetic 5-nonyloxytryptamine protects cerebellar neurons against glutamate induced excitotoxicity: An in vitro perspective

Journal

NEUROTOXICOLOGY
Volume 82, Issue -, Pages 69-81

Publisher

ELSEVIER
DOI: 10.1016/j.neuro.2020.11.003

Keywords

Glutamate excitotoxicity; 5-Nonyloxytryptamine; PSA-NCAM; Synaptic plasticity; Neuroprotection; Neurodegeneration

Funding

  1. DST-SERB, Government of India (GOI) [EMR/2016/002416]

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The study found that 5-NOT may serve as a potential neuroprotective candidate by promoting axonal growth and migration of neurons, as well as regulating the expression of synaptic plasticity and cell survival pathway proteins.
PSA-NCAM is a molecule of therapeutic interest for its key role in promoting neuritogenesis and synaptic plasticity. The current study was aimed to investigate the neuroregenerative potential of 5-nonyloxytryptamine (5-NOT) as PSA mimetic compound against glutamate induced excitotoxicity. 2D and 3D cultures of cerebellar neurons challenged with glutamate were used to ascertain the effect of 5-NOT on neurite outgrowth, migration and expression of neuronal plasticity markers. Glutamate excitotoxicity is one of the major underlying pathological factor responsible for neurodegeneration in various neurological disorders such as trauma, stroke, ischemia, epilepsy and neurodegenerative diseases.5-NOT treatment was observed to promote axonal growth and defasiculation in glutamate challenged neurons as well as promoted the migration of cerebellar neurons in both wound scratched area and cerebellar explant cultures. Further, 5-NOT treatment upregulated the expression of synaptic plasticity and cell survival pathway proteins which showed reduced expression after glutamate induced excitotoxicity. Thus, this preliminary data reveals thatPSA-mimetic,5-NOT may prove to be a potential neuroprotective candidate for neurodegenerative diseases.

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