组织选择性粉样蛋白疾病的生物和化学基础
Yoshiki Sekijima1, R Luke Wiseman, Jeanne Matteson
1Department of Chemistry, The Skaggs Institute of Chemical Biology, The Skaggs Research Institute, 10550 N. Torrey Pines Road, BCC506, La Jolla, California 92037, USA.
Cell
|April 12, 2005
概括
哺乳动物细胞有效地分泌TTR变体,即使折叠不良. 蛋白质折叠的能量,而不仅仅是稳定性,决定了分泌与降解,解释了组织特异性氨基粉症.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 细胞外粉样蛋白疾病的发病和进展因素尚不清楚.
- 细胞内膜网膜 (ER) 机制在准错误折叠的蛋白质进行降解方面的作用至关重要.
- 分泌的蛋白质变体往往表现出增强的聚合倾向.
研究的目的:
- 调查控制跨甲状腺素 (TTR) 变种分泌和降解的因素.
- 了解蛋白质折叠能量在ER相关降解 (ERAD) 与ER辅助折叠和出口 (ERAF) 中的作用.
- 阐明组织选择性氨基粉症背后的机制.
主要方法:
- 利用哺乳动物细胞培养系统研究TTR变异分泌.
- 分析了TTR变体的蛋白质折叠能量和稳定性.
- 研究了ERAD和ERAF路径之间的相互作用.
主要成果:
- 哺乳动物细胞分泌各种与TTR疾病相关的变体,具有野生类型的效率,尽管折叠受损.
- 只有高度不稳定的TTR变种才会经历ERAD,而这是组织特异性的.
- 基于全球蛋白质能量的ER-辅助折叠 (ERAF) 控制了蛋白质出口效率.
结论:
- 受到蛋白质能量和细胞因素的影响,ERAD和ERAF决定了蛋白质的分泌命运.
- 在ERAF和ERAD的组织特异性差异有助于对粉样化症的敏感性变化.
- 蛋白质折叠能量,而不是严格的稳定性值,决定了ER出口与降解.
相关概念视频
03:03Amyloid Fibrils
11.7K
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,...
11.7K
03:03Amyloid Fibrils
6.4K
No description available
6.4K
01:57What is Conservation Biology?
24.0K
Conservation biology is a scientific field that focuses on the preservation of biodiversity in order to protect ecosystems while meeting the needs of the human population. Humans require properly functioning ecosystems to maintain our supply of natural resources, including food, medicines, and building materials.
24.0K
02:59Biological Effects of Radiation
17.7K
All radioactive nuclides emit high-energy particles or electromagnetic waves. When this radiation encounters living cells, it can cause heating, break chemical bonds, or ionize molecules. The most serious biological damage results when these radioactive emissions fragment or ionize molecules. For example, α and β particles emitted from nuclear decay reactions possess much higher energies than ordinary chemical bond energies. When these particles strike and penetrate matter, they...
17.7K
02:52Chemical Formulas
61.1K
A chemical formula presents information about the proportions of atoms constituting a particular chemical compound or molecule, mainly using symbols of elements and numbers. At times other symbols, such as dashes, parentheses, brackets, commas, plus, and minus signs, are also used. A chemical formula can be one of three types – molecular, empirical, and structural.
61.1K
03:10Chemical Equations
80.9K
Chemical equations represent the identities and relative quantities of substances involved in a chemical reaction. The substances undergoing reaction are called reactants, and their formulas are placed on the left side of the equation. The substances generated by the reaction are called products, and their formulas are placed on the right side of the equation. Plus signs (+) separate individual reactant and product formulas, and an arrow (→) separates the reactant and product (left and right)...
80.9K