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Somatic to iPS Cell Reprogramming01:29

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Reprogramming alters the gene expression in somatic cells, transforming them into induced pluripotent stem (iPS) cells over several generations. Scientists can reprogram cells by introducing genes for four transcription factors—Oct4, Sox2, Klf4, and c-Myc (OSKM) by viral or non-viral methods. These factors are also known as Yamanaka factors after Shinya Yamanaka, who first generated iPS cells using mouse skin cells. Yamanaka was awarded the Nobel Prize in Physiology or Medicine in 2012...
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Nuclear reprogramming is a process of transforming one cell type into an unrelated cell type by epigenetic changes that alter the cell’s original gene expression pattern. Such epigenetic changes force cells to express a different set of genes, which play a significant role in inducing transformation into other cell types. Nuclear reprogramming offers applications in reproductive cloning for livestock propagation and regenerative medicine — developing patient-specific cells for...
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Nuclear reprogramming is the process of switching gene expression of one cell type to that of another cell type, usually from a differentiated cell state to an undifferentiated cell state. Differentiation occurs during processes such as development and morphogenesis, tissue regeneration, and malignancy. Cells can also be artificially induced to reprogram their gene expression by techniques such as nuclear transfer, induced pluripotency, and cell fusion. Such techniques have many applications in...
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Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
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Chemogenetic Regulation in Reprogrammed Stem Cell-derived Precursor Cells in Treating Neurodegenerative Diseases
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一个人工蛋白质调节器重新编程神经元蛋白质功能.

Peihua Lin1,2, Bo Zhang1,3, Hongli Yang2

  • 1Frontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, School of Biomedical Engineering, National Center for Translational Medicine, State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University, Shanghai, 200240, China.

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人工蛋白调节器 (APROM) 的设计是为了逆转异常蛋白质酸化,这是疾病中的一个关键过程. 这些APROM通过向高酸化蛋白来恢复帕金森病模型中的突触功能.

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科学领域:

  • 生物化学 生物化学
  • 化学生物学 化学生物学
  • 神经科学是一个神经科学.

背景情况:

  • 可逆蛋白质酸化对细胞功能至关重要,由蛋白质酸酶调节.
  • 酸化失调导致异常的翻译后修饰 (PTM) 和疾病.
  • 直接调节蛋白质的人工催化剂尚未得到充分的研究.

研究的目的:

  • 开发人工蛋白调节器 (APROM) 用于逆转异常的PTM.
  • 为了实现对治疗应用的蛋白质功能的精确控制.
  • 调查APROM在神经疾病模型中的有效性.

主要方法:

  • 具有不对称中心的异质催化剂的原子级工程.
  • 设计具有与蛋白质酸酶结构和功能相似性的APROM.
  • 评估APROMs对基质水解和重新编程蛋白质功能的能力.

主要成果:

  • 开发的APROM具有类似蛋白酸酶的特征.
  • APROMs有效地破坏了桥梁μ3-氧化物的稳定,激活了催化中心.
  • 在帕金森病模型中,APROMs通过化高酸化形式来催化地重新编程α-synuclein,从而增强了帕金森病模型中的突触功能.

结论:

  • APROM为新的PTM和蛋白质功能重编程提供了一种新的策略.
  • 这种方法有望开发与异常酸化相关的疾病的新疗法.
  • 蛋白质PTMs的直接催化调制代表了化学生物学中的重大进步.