驱动一个转录适应程序来阻断铁和治疗中风
Ishraq Alim1, Joseph T Caulfield1, Yingxin Chen1
1Sperling Center for Hemorrhagic Stroke Recovery, Burke Neurological Institute at Weill Cornell Medicine, White Plains, NY 10605, USA; Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY 10065, USA.
Cell
|May 7, 2019
概括
补充剂可以促进神经元中抗氧化剂GPX4的表达,保护神经元免受铁亡和其他细胞死亡形式的侵害. 这一发现为神经系统疾病 (如中风) 提供了新的治疗途径.
科学领域:
- 神经科学是一个神经科学.
- 细胞生物学 细胞生物学
- 生物化学 生化学
背景情况:
- 铁亡是一种被编程的细胞死亡途径,涉及到各种疾病,包括中风.
- 之前还没有发现对铁亡的协调转录反应.
- 神经元在特定的压力条件下易受铁亡.
研究的目的:
- 为了研究神经元对ferroptotic刺激的恒常转录反应.
- 探索和蛋白在神经元保护细胞死亡中的作用.
- 评估补充剂在神经疾病中的治疗潜力.
主要方法:
- 在神经元模型中诱导铁亡.
- 对基因表达的分析,专注于单蛋白和转录因子 (TFAP2c,Sp1).
- (Se) 和一种的药理管理.
- 在出血性中风模型中评估神经元存活率和功能恢复.
主要成果:
- 神经元对铁灭产生转录性反应,诱导诸如谷氨过氧化酶4 (GPX4) 等单蛋白.
- 补充剂通过TFAP2c和Sp1激活增强GPX4和其他基因,保护神经元.
- 在中风模型中,单次的大脑剂量Se可以保护神经元并改善行为.
- 药理性Se抑制了GPX4依赖的铁和GPX4独立的细胞死亡 (兴奋毒性,ER压力).
- 在中风后,系统地给药一种胺会抑制细胞死亡并改善功能.
结论:
- 药理激活神经保护性转录程序,抑制多个细胞死亡途径.
- 补充剂代表了对中风和潜在的其他神经系统疾病的有希望的治疗策略.
- 向单体提供了一种新的方法来对抗神经元细胞死亡.
相关概念视频
02:16Transcription Factors
82.3K
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
82.3K
01:10Transcription
155.9K
Overview
Transcription is the process of synthesizing RNA from a DNA sequence by RNA polymerase. It is the first step in producing a protein from a gene sequence. Additionally, many other proteins and regulatory sequences are involved in the proper synthesis of messenger RNA (mRNA). Regulation of transcription is responsible for the differentiation of all the different types of cells and often for the proper cellular response to environmental signals.
Transcription Can Produce Different Kinds...
Transcription is the process of synthesizing RNA from a DNA sequence by RNA polymerase. It is the first step in producing a protein from a gene sequence. Additionally, many other proteins and regulatory sequences are involved in the proper synthesis of messenger RNA (mRNA). Regulation of transcription is responsible for the differentiation of all the different types of cells and often for the proper cellular response to environmental signals.
Transcription Can Produce Different Kinds...
155.9K
01:52Eukaryotic Transcription Inhibitors
10.9K
Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
10.9K
01:37Energy to Drive Translocation
2.7K
Mitochondrial protein import is powered by two distinct energy sources: ATP hydrolysis and electrochemical potential across the inner membrane. Newly synthesized precursors are bound by cytosolic chaperones of the Hsp70 family, which guide them to the import receptors on the mitochondrial surface. Utilizing the energy of ATP hydrolysis, Hsp70 chaperones transfer these precursors to the TOM receptors on the mitochondrial outer membrane.
Generally, polypeptides are unfolded by two distinct...
Generally, polypeptides are unfolded by two distinct...
2.7K
01:58Prokaryotic Transcriptional Activators and Repressors
25.2K
The organization of prokaryotic genes in their genome is notably different from that of eukaryotes. Prokaryotic genes are organized, such that the genes for proteins involved in the same biochemical process or function are located together in groups. This group of genes, along with their regulatory elements, are collectively known as an operon. The functional genes in an operon are transcribed together to give a single strand of mRNA known as polycistronic mRNA.
Transcription of prokaryotic...
Transcription of prokaryotic...
25.2K
02:23Master Transcription Regulators
7.7K
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
7.7K