在老龄化的老鼠模型中,认知相关的蛋白质结构变化与减少重新折叠能力有关
Haley E Tarbox1, Audrey Branch2, Stephen D Fried1,3
1Department of Chemistry, Johns Hopkins University, Baltimore, MD 21218, USA.
bioRxiv : the preprint server for biology
|October 10, 2024
概括
衰老会损害蛋白质结构,导致认知能力下降. 这项研究表明,非粉样蛋白错误折叠与老年相关的老鼠认知障碍有关.
科学领域:
- 神经科学是一个神经科学.
- 蛋白质组学是指蛋白质组学.
- 衰老研究研究 衰老研究
背景情况:
- 老龄化中的认知衰退是一个重要的社会问题.
- 虽然已知β-粉样蛋白和α-synuclein随着年龄的增长而错误折叠,但受损的蛋白质稳定性表明其他蛋白质也可能发生变化.
- 与年龄相关的蛋白质结构变化可能导致认知障碍.
研究的目的:
- 在认知衰老的老鼠模型中研究全球蛋白质构造变化.
- 在海马体中识别具有认知相关结构变化 (CASCs) 的蛋白质.
- 为了确定蛋白质的非折叠性是否与认知能力下降有关.
主要方法:
- 利用有限蛋白解质质谱法 (LiP-MS),一种结构蛋白质组技术.
- 对比了老老老鼠的可溶性海马蛋白质,这些老鼠的认知能力得到了保护,而认知能力受损.
- 分析了像氧化和酸化这样的翻译后修改,以排除混杂效应.
主要成果:
- 确定了几百种表现出认知相关结构变化的蛋白质 (CASC).
- 与非CASC相比,含有CASC的蛋白质具有明显更高的非可折叠性.
- 翻译后的修改没有实质性地解释观察到的结构变化.
结论:
- 蛋白质的非共价性,构造性变化可能是认知衰退的一般特征.
- 与认知衰老相关的蛋白质错折不需要粉样蛋白的形成.
- 结构性蛋白质变化,超出已知的粉样蛋白,与与年龄相关的认知恶化有关.
更多相关视频
11:57Methods to Study Changes in Inherent Protein Aggregation with Age in Caenorhabditis elegans
Published on: November 26, 2017
8.5K
14:57Preparation of Acute Hippocampal Slices from Rats and Transgenic Mice for the Study of Synaptic Alterations during Aging and Amyloid Pathology
Published on: March 23, 2011
94.0K
相关概念视频
03:03Amyloid Fibrils
9.3K
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,...
9.3K
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
01:26Aging
37
Aging is a complex biological phenomenon influenced by various processes that affect cellular and systemic functions. Several prominent theories attempt to explain its mechanisms, highlighting cellular limitations, oxidative damage, and hormonal changes as central factors in aging.
Cellular Clock Theory
The cellular clock theory posits that the human lifespan is closely tied to the finite capacity of cells to divide, a phenomenon governed by telomeres, which are protective caps at the ends of...
Cellular Clock Theory
The cellular clock theory posits that the human lifespan is closely tied to the finite capacity of cells to divide, a phenomenon governed by telomeres, which are protective caps at the ends of...
37