相关实验视频

Updated: Jul 4, 2025

Live Imaging of Mitosis in the Developing Mouse Embryonic Cortex

Live Imaging of Mitosis in the Developing Mouse Embryonic Cortex

Published on: June 4, 2014

在小鼠大脑中,细胞类型特定的CDKL5活动的表达,调节和补偿

Margaux Silvestre¹, Kelvin Dempster¹, Simeon R Mihaylov¹

¹Kinases and Brain Development Laboratory, The Francis Crick Institute, London, UK.

Molecular psychiatry

|February 7, 2024

概括

循环素依赖性酶类5 (CDKL5) 缺乏障碍疗法可能是可能的. CDKL2激酶可以补偿大脑中的CDKL5损失,提供新的治疗途径.

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:

CDKL5缺乏症 (CDD) 是一种严重的神经发育状况.
了解CDKL5的表达和活性对于开发向疗法至关重要.

研究的目的:

为了研究CDKL5在大脑中的表达和活动.
确定CDD中潜在的补偿机制.

主要方法:

在特定的神经元类型和星球细胞中生成条件Cdkl5淘汰赛小鼠.
利用化EB2 (CDKL5基质) 的固特异性抗体来评估酶活性.
选候选激酶并生成双淘汰赛小鼠 (Cdkl5/Cdkl2) 来测试补偿酸化.

主要成果:

CDKL5和EB2酸化在激发性和抑制性神经元中突出,但在星球细胞中并非如此.
在Cdkl5淘汰模式中,EB2酸化的残留15-20%仍然存在.
鉴定出CDKL2和ICK是能够酸化EB2 S222.22的激酶.
在双淘汰赛小鼠体内,CDKL2被证实能化CDKL5基质.

结论:

CDKL5主要表达在神经元和酸化物EB2.
CDKL2可以通过在大脑中酸化其基质来补偿CDKL5的功能.
这种CDKL2的补偿作用表明了CDD的新疗法策略.

更多相关视频

Induction of Protein Deletion Through In Utero Electroporation to Define Deficits in Neuronal Migration in Transgenic Models

Induction of Protein Deletion Through In Utero Electroporation to Define Deficits in Neuronal Migration in Transgenic Models

Published on: January 12, 2015

Expansion of Embryonic and Adult Neural Stem Cells by In Utero Electroporation or Viral Stereotaxic Injection

Expansion of Embryonic and Adult Neural Stem Cells by In Utero Electroporation or Viral Stereotaxic Injection

Published on: October 6, 2012

相关概念视频

Positive Regulator Molecules

Positive Regulator Molecules

Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.

Inhibition of Cdk Activity

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...

M-Cdk Drives Transition Into Mitosis

M-Cdk Drives Transition Into Mitosis

Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...