在蛋白质聚合和神经退行性疾病中的非酶性翻译后蛋白质修饰
Tim Baldensperger1, Miriam Preissler1,2, Christian F W Becker1
1University of Vienna, Faculty of Chemistry, Institute of Biological Chemistry Währinger Str. 38 1090 Vienna Austria tim.baldensperger@univie.ac.at miriam.preissler@univie.ac.at christian.becker@univie.ac.at.
RSC chemical biology
|December 26, 2024
概括
非酶的翻译后修饰 (nPTMs) 在老化蛋白质中积累,影响神经退行性疾病. 这篇评论探讨了阿尔茨海默氏症和帕金森症中的nPTM,讨论了它们在蛋白质聚合和细胞功能障碍中的作用.
科学领域:
- 生物化学 生物化学
- 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:
- 非酶的翻译后修饰 (nPTMs) 产生于修饰蛋白氨基酸侧链的反应分子.
- 在代谢压力下,nPTMs增加,并且可以改变蛋白质结构和功能,在长寿命蛋白质中积累.
- nPTM与衰老和糖尿病和白内障等疾病有关,它们在神经退行 (阿尔茨海默病,帕金森病) 中的作用是一个关键的研究问题.
研究的目的:
- 对神经退行性疾病 (α-synuclein,β-amyloid,tau) 中心的蛋白质进行主要nPTM的审查.
- 要总结nPTM的形成,它们对疾病发病/进展的影响以及对细胞系统的影响.
- 讨论研究NPTM及其在蛋白质聚合中的作用的方法.
主要方法:
- 文献综述重点关注关键神经退行性疾病蛋白中的nPTMs.
- 对nPTM形成和细胞影响现有知识的分析.
- 对当前的方法和建议的先进技术进行批判性讨论.
主要成果:
- nPTMs显著影响像α-synuclein,β-amyloid和tau这样的蛋白质,这些蛋白质与神经退行有关.
- 积累nPTMs可以损害细胞解毒,修复和降解途径.
- 讨论了nPTM调查的现有方法,强调了其局限性.
结论:
- nPTM是神经退行性疾病发病的关键因素,影响蛋白质聚合和细胞健康.
- 需要先进的化学和分子生物学技术,包括特定地点的修改,以进一步阐明nPTM的作用.
- 增加对nPTM的研究,适应酶修饰研究方法,对于理解和潜在地治疗神经退行至关重要.
相关概念视频
03:03Amyloid Fibrils
9.2K
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,...
9.2K
02:04Covalently Linked Protein Regulators
6.8K
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.
These groups modify specific amino acids in a protein....
These groups modify specific amino acids in a protein....
6.8K
01:26Protein Modifications in the RER
5.0K
Modification of secretory and transmembrane proteins entering the rough ER begins in the ER lumen. These modifications aid in protein folding and stabilize the acquired tertiary structure. Protein modifications in the rough ER co-occur at different stages of protein folding.
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal...
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal...
5.0K
01:25Protein Glycosylation
6.8K
Glycosylation, the most common post-translational modification for proteins, serves diverse functions. Adding sugars to proteins makes the proteins more resistant to proteolytic digestion. Glycosylated proteins can act as markers and receptors to promote cell-cell adhesion. Additionally, they have many essential quality control functions in the cell, such as correct protein folding and facilitating transport of misfolded proteins to the cytosol, which can be degraded.
Glycosylation occurs in...
Glycosylation occurs in...
6.8K
02:11Proteins: From Genes to Degradation
12.0K
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...
12.0K
01:13The Proteasome
813
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...
813