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PSA 拟似物 5-壬氧基色胺可防止谷氨酸诱导的小脑神经元兴奋性毒性:体外研究视角。

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

机构信息

Department of Biotechnology, Guru Nanak Dev University, Amritsar, Punjab, 143005, India.

出版信息

Neurotoxicology. 2021 Jan;82:69-81. doi: 10.1016/j.neuro.2020.11.003. Epub 2020 Nov 13.

Abstract

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.

摘要

PSA-NCAM 是一种具有治疗潜力的分子,因为它在促进神经突生成和突触可塑性方面发挥着关键作用。本研究旨在研究 5-正壬氧基色胺(5-NOT)作为 PSA 模拟化合物对谷氨酸诱导的兴奋性毒性的神经再生潜力。使用与谷氨酸孵育的小脑神经元的 2D 和 3D 培养物,以确定 5-NOT 对神经突生长、迁移和神经元可塑性标志物表达的影响。谷氨酸兴奋性毒性是导致各种神经退行性疾病(如创伤、中风、缺血、癫痫和神经退行性疾病)中神经退行性变的主要潜在病理因素之一。观察到 5-NOT 处理可促进谷氨酸挑战神经元中的轴突生长和去极化,以及促进小脑神经元在划痕区域和小脑外植体培养物中的迁移。此外,5-NOT 处理上调了突触可塑性和细胞存活途径蛋白的表达,这些蛋白在谷氨酸诱导的兴奋性毒性后表达减少。因此,这些初步数据表明,PSA 模拟物 5-NOT 可能是神经退行性疾病的潜在神经保护候选物。

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