{"title":"Uncovering Cell Cycle Dysregulations and Associated Mechanisms in Cancer and Neurodegenerative Disorders: A Glimpse of Hope for Repurposed Drugs.","authors":"Dia Advani, Pravir Kumar","doi":"10.1007/s12035-024-04130-7","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"8600-8630"},"PeriodicalIF":4.3000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Neurobiology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s12035-024-04130-7","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/3/26 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0
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.
细胞周期是由复杂的细胞周期蛋白网络协调的一系列事件。与正常细胞不同,成熟的神经元处于细胞周期的静止状态,异常的细胞周期激活会引发神经元死亡并伴随神经变性。细胞周期事件的周期性由各种机制编排,包括 DNA 损伤修复、氧化应激、神经营养素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疾病中的相关性,本综述描述了与癌症和主要神经退行性疾病中细胞周期畸变相关的重叠细胞周期事件、信号通路和机制。我们认为,一些共同的基本信号转导过程失调会引发癌细胞和神经元中异常的细胞周期激活。我们讨论了细胞周期抑制剂用于神经退行性疾病的可能性,并描述了相关的挑战。我们认为,进一步了解癌症和神经退行性疾病中细胞周期畸变的共同驱动机制,将为开发具有新用途的药物开辟一条新途径。
期刊介绍:
Molecular Neurobiology is an exciting journal for neuroscientists needing to stay in close touch with progress at the forefront of molecular brain research today. It is an especially important periodical for graduate students and "postdocs," specifically designed to synthesize and critically assess research trends for all neuroscientists hoping to stay active at the cutting edge of this dramatically developing area. This journal has proven to be crucial in departmental libraries, serving as essential reading for every committed neuroscientist who is striving to keep abreast of all rapid developments in a forefront field. Most recent significant advances in experimental and clinical neuroscience have been occurring at the molecular level. Until now, there has been no journal devoted to looking closely at this fragmented literature in a critical, coherent fashion. Each submission is thoroughly analyzed by scientists and clinicians internationally renowned for their special competence in the areas treated.