4.6 Article

The Role of the Ubiquitin Proteasome System in Glioma: Analysis Emphasizing the Main Molecular Players and Therapeutic Strategies Identified in Glioblastoma Multiforme

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MOLECULAR NEUROBIOLOGY
卷 58, 期 7, 页码 3252-3269

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SPRINGER
DOI: 10.1007/s12035-021-02339-4

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Glioma; Ubiquitin; Proteasome; E3 ligase; Deubiquitinases; PROTACs

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Gliomas are the most common tumors in the brain, especially high-grade ones with poor prognosis and difficulty in treatment. Modulation of protein degradation through the ubiquitin proteasome system is being studied as a potential mechanism for controlling gliomas by regulating different cellular mechanisms in tumors.
Gliomas constitute the most frequent tumors of the brain. High-grade gliomas are characterized by a poor prognosis caused by a set of attributes making treatment difficult, such as heterogeneity and cell infiltration. Additionally, there is a subgroup of glioma cells with properties similar to those of stem cells responsible for tumor recurrence after treatment. Since proteasomal degradation regulates multiple cellular processes, any mutation causing disturbances in the function or expression of its elements can lead to various disorders such as cancer. Several studies have focused on protein degradation modulation as a mechanism of glioma control. The ubiquitin proteasome system is the main mechanism of cellular proteolysis that regulates different events, intervening in pathological processes with exacerbating or suppressive effects on diseases. This review analyzes the role of proteasomal degradation in gliomas, emphasizing the elements of this system that modulate different cellular mechanisms in tumors and discussing the potential of distinct compounds controlling brain tumorigenesis through the proteasomal pathway.

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