Role of Glutamate Excitotoxicity in Glioblastoma Growth and Its Implications in Treatment.

IF 3.3 3区 生物学 Q3 CELL BIOLOGY
Colin Moriarty, Natasha Gupta, Debanjan Bhattacharya
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引用次数: 0

Abstract

Glioblastoma is a highly malignant and invasive type of primary brain tumor that originates from astrocytes. Glutamate, a neurotransmitter in the brain plays a crucial role in excitotoxic cell death. Excessive glutamate triggers a pathological process known as glutamate excitotoxicity, leading to neuronal damage. This excitotoxicity contributes to neuronal death and tumor necrosis in glioblastoma, resulting in seizures and symptoms such as difficulty in concentrating, low energy, depression, and insomnia. Glioblastoma cells, derived from astrocytes, fail to maintain glutamate-glutamine homeostasis, releasing excess glutamate into the extracellular space. This glutamate activates ionotropic N-methyl-D-aspartate (NMDA) receptors and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors on nearby neurons, causing hyperexcitability and triggering apoptosis through caspase activation. Additionally, glioblastoma cells possess calcium-permeable AMPA receptors, which are activated by glutamate in an autocrine manner. This activation increases intracellular calcium levels, triggering various signaling pathways. Alkylating agent temozolomide has been used to counteract glutamate excitotoxicity, but its efficacy in directly combating excitotoxicity is limited due to the development of resistance in glioblastoma cells. There is an unmet need for alternative biochemical agents that can have the greatest impact on reducing glutamate excitotoxicity in glioblastoma. In this review, we discuss the mechanism and various signaling pathways involved in glutamate excitotoxicity in glioblastoma cells. We also examine the roles of various receptor and transporter proteins, in glutamate excitotoxicity and highlight biochemical agents that can mitigate glutamate excitotoxicity in glioblastoma and serve as potential therapeutic agents.

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来源期刊
Cell Biology International
Cell Biology International 生物-细胞生物学
CiteScore
7.60
自引率
0.00%
发文量
208
审稿时长
1 months
期刊介绍: Each month, the journal publishes easy-to-assimilate, up-to-the minute reports of experimental findings by researchers using a wide range of the latest techniques. Promoting the aims of cell biologists worldwide, papers reporting on structure and function - especially where they relate to the physiology of the whole cell - are strongly encouraged. Molecular biology is welcome, as long as articles report findings that are seen in the wider context of cell biology. In covering all areas of the cell, the journal is both appealing and accessible to a broad audience. Authors whose papers do not appeal to cell biologists in general because their topic is too specialized (e.g. infectious microbes, protozoology) are recommended to send them to more relevant journals. Papers reporting whole animal studies or work more suited to a medical journal, e.g. histopathological studies or clinical immunology, are unlikely to be accepted, unless they are fully focused on some important cellular aspect. These last remarks extend particularly to papers on cancer. Unless firmly based on some deeper cellular or molecular biological principle, papers that are highly specialized in this field, with limited appeal to cell biologists at large, should be directed towards journals devoted to cancer, there being very many from which to choose.
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