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揭示癌症和神经退行性疾病中的细胞周期失调及其相关机制:重新利用药物的一线曙光。

Uncovering Cell Cycle Dysregulations and Associated Mechanisms in Cancer and Neurodegenerative Disorders: A Glimpse of Hope for Repurposed Drugs.

机构信息

Molecular Neuroscience and Functional Genomics Laboratory, Department of Biotechnology, Delhi Technological University (Formerly Delhi College of Engineering), Shahbad Daulatpur, Bawana Road, New Delhi, Delhi, 110042, India.

出版信息

Mol Neurobiol. 2024 Nov;61(11):8600-8630. doi: 10.1007/s12035-024-04130-7. Epub 2024 Mar 26.

Abstract

The cell cycle is the sequence of events orchestrated by a complex network of cell cycle proteins. Unlike normal cells, mature neurons subsist in a quiescent state of the cell cycle, and aberrant cell cycle activation triggers neuronal death accompanied by neurodegeneration. The periodicity of cell cycle events is choreographed by various mechanisms, including DNA damage repair, oxidative stress, neurotrophin activity, and ubiquitin-mediated degradation. Given the relevance of cell cycle processes in cancer and neurodegeneration, this review delineates the overlapping cell cycle events, signaling pathways, and mechanisms associated with cell cycle aberrations in cancer and the major neurodegenerative disorders. We suggest that dysregulation of some common fundamental signaling processes triggers anomalous cell cycle activation in cancer cells and neurons. We discussed the possible use of cell cycle inhibitors for neurodegenerative disorders and described the associated challenges. We propose that a greater understanding of the common mechanisms driving cell cycle aberrations in cancer and neurodegenerative disorders will open a new avenue for the development of repurposed drugs.

摘要

细胞周期是由细胞周期蛋白的复杂网络精心编排的一系列事件。与正常细胞不同,成熟神经元处于细胞周期的静止状态,细胞周期的异常激活会引发神经元死亡和神经退行性变。细胞周期事件的周期性是由各种机制协调的,包括 DNA 损伤修复、氧化应激、神经营养因子活性和泛素介导的降解。鉴于细胞周期过程在癌症和神经退行性变中的相关性,本综述描述了癌症和主要神经退行性疾病中与细胞周期异常相关的细胞周期事件、信号通路和机制的重叠。我们认为,一些常见基本信号过程的失调会触发癌细胞和神经元异常的细胞周期激活。我们讨论了细胞周期抑制剂在神经退行性疾病中的可能用途,并描述了相关挑战。我们提出,对驱动癌症和神经退行性疾病细胞周期异常的共同机制有更深入的了解,将为重新利用药物的开发开辟新途径。

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