miR-449a细胞循环机制的中介抑制可以防止神经元亡
Monika Chauhan1, Komal Singh1, Chen Chongtham2
1Eukaryotic Gene Expression Laboratory, National Institute of Immunology, New Delhi, India.
The Journal of biological chemistry
|August 22, 2024
概括
微RNA-449a抑制神经元细胞循环激活,防止阿尔茨海默氏症患者的亡.
科学领域:
- 神经科学是一个神经科学.
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 异常的神经元细胞周期激活导致神经退行性疾病如阿尔茨海默氏症 (AD) 中的神经细胞亡和神经元损失.
- 调节细胞循环相关的神经细胞亡的机制仍然不太了解.
研究的目的:
- 调查失调的微RNAs (miRNAs) 在阿尔茨海默病中神经元亡中的作用.
- 阐明miR-449a在神经元细胞循环调节中的功能及其在AD中的潜在治疗应用.
主要方法:
- 从阿尔茨海默病 (TgAD) 的转基因小鼠模型的神经元中鉴定出失调的miRNAs.
- 研究了miR-449a对神经元分化,细胞循环和细胞亡的影响.
- 评估了miR-449a针对细胞周期基因 (cyclin D1,CDC25A) 的影响.
- 评估了lentiviral介导的miR-449a在TgAD小鼠中的治疗潜力.
主要成果:
- 发现包括miR-449a在内的几种miRNA在TgAD小鼠神经元中失调,并预测将向细胞周期基因.
- miR-449a通过抑制细胞循环促进神经元分化,其表达受到粉样β 42 (Aβ42) 的影响.
- 损失miR-449a导致细胞周期激活和细胞亡;其向cyclin D1和CDC25A被确定.
- 在TgAD小鼠中服用miR-449a的lentiviral药物显著改善了学习和记忆缺陷.
结论:
- miR-449a在预防阿尔茨海默病中细胞周期相关的神经元亡方面发挥着至关重要的作用.
- 恢复miR-449a水平可能通过改善认知衰退和神经元损失,为阿尔茨海默病提供治疗策略.
更多相关视频
相关概念视频
01:23Negative Regulator Molecules
35.2K
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
35.2K
02:23Abnormal Proliferation
4.5K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.5K
01:28The Cell Cycle Control System
2.7K
The cell cycle regulation directs how a cell proceeds from one phase to the next and begins mitosis. The cell cycle control system includes intracellular regulatory molecules and external triggers. They provide "stop" or "advance" signals and operate at specific cell cycle stages termed checkpoints to ensure that a particular process is completed before the cell advances to the next phase.
Cyclins and cyclin-dependent kinases (Cdks) are the primary cell cycle regulators and...
Cyclins and cyclin-dependent kinases (Cdks) are the primary cell cycle regulators and...
2.7K
01:27Molecular Factors Affecting Cell Division
3.0K
Several external and internal factors influence the initiation and inhibition of cell division. For instance, the death of nearby cells or the release of human growth hormone (hGH) promotes cell division. In contrast, lack of hGH or crowding of cells can inhibit cell division.
Several proteins function as internal regulators to ensure each cell cycle stage is completed faithfully before proceeding to the next. Regulator molecules may act directly or influence the activity or production of other...
Several proteins function as internal regulators to ensure each cell cycle stage is completed faithfully before proceeding to the next. Regulator molecules may act directly or influence the activity or production of other...
3.0K
01:22MicroRNAs
3.0K
MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
3.0K
02:37DNA Damage can Stall the Cell Cycle
9.1K
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
9.1K