在衰老的脊椎动物中,蛋白质聚合和质量控制的特定组织格局
Yiwen R Chen1, Itamar Harel2, Param Priya Singh3
1Department of Chemical and Systems Biology, Stanford University, Stanford, CA 94305, USA.
Developmental cell
|May 29, 2024
概括
在衰老过程中蛋白质聚合是组织特异性的,而不仅仅是在大脑中. 这项研究揭示了与蛋白质特征和质量控制的联系,影响与年龄相关的疾病.
科学领域:
- 老年学是指老年学的学科.
- 分子生物学分子生物学
- 神经科学是一个神经科学.
背景情况:
- 蛋白质聚合是与年龄相关的神经退行性疾病的关键特征.
- 在非大脑组织和正常衰老过程中对蛋白质聚合的理解是有限的.
研究的目的:
- 在一个衰老的脊椎动物模型中,系统地对7个组织中的蛋白质聚合物进行分析.
- 调查依赖年龄的蛋白质聚合的组织特异性及其潜在机制.
主要方法:
- 利用非洲绿色鱼作为老化研究的模型生物.
- 在鱼和酵母中采用实验性询问,并采用机器学习方法.
- 分析了蛋白质表达,生物物理性质和蛋白质质量控制变化.
主要成果:
- 年龄依赖的蛋白质聚合表现出惊人的组织特异性,不仅仅是由蛋白质表达水平驱动的.
- 特异性与蛋白质自主生物物理特征和蛋白质质量控制中的组织特异性变化有关.
- 蛋白质质量控制机制的联合聚合可能会降低老化过程中的蛋白质稳定能力.
- 一个孕病模型显示,在加速衰老的组织中选择性增加聚合.
- 识别了野生类型的蛋白质,形成聚合物,当它们发生突变时,会导致人类疾病.
结论:
- 在衰老过程中蛋白质聚合是一种复杂的,组织特异性的现象.
- 蛋白质的生物物理特性和组织特异性的蛋白质稳定机制是聚合的关键决定因素.
- 这些发现提供了老化脊椎动物蛋白质聚合的全面地图,以及其与功能障碍和疾病的关联.
相关概念视频
01:29Protein Folding Quality Check in the RER
3.7K
ER is the primary site for the maturation and folding of soluble and transmembrane secretory proteins. The calnexin cycle is a specific chaperone system that folds and assesses the confirmation of N-glycosylated proteins before they can exit the ER lumen. The primary players of this quality check pipeline are the lectins, ER-resident chaperones, and a glucosyl transferase enzyme. In case the calnexin system in the lumen fails to salvage a misfolded protein, it is transported to the cytoplasm...
3.7K
03:03Amyloid Fibrils
9.5K
Amyloid fibrils are aggregates of misfolded proteins. Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils.
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
9.5K
02:58Regulated Protein Degradation
7.2K
It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
7.2K
02:11Proteins: From Genes to Degradation
12.2K
Within a biological system, the DNA encodes the RNA, and the nucleotide sequence in the RNA further defines the amino acid sequence in the protein. This is referred to as “The Central Dogma of Molecular Biology” - a term coined by Francis Crick. Central dogma is a firm principle in biology that defines the flow of genetic information within any life form. The two fundamental steps in central dogma are - transcription and translation.
Transcription is the synthesis of RNA...
Transcription is the synthesis of RNA...
12.2K
01:13The Proteasome
830
Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
830