通过 lysosomal 途径针对蛋白质降解的策略
Wei Wang1, Yuxin Fang1, Chunquan Sheng1
1The Center for Basic Research and Innovation of Medicine and Pharmacy (MOE), School of Pharmacy, Second Military Medical University (Naval Medical University), Shanghai 200433, People's Republic of China.
Advanced drug delivery reviews
|February 25, 2026
概括
向蛋白解酶的仿真体 (PROTACs) 在降解某些蛋白质方面面临限制. lysosome-engaging targeted protein degradation (TPD) 策略为克服这些挑战和扩大治疗应用提供了一个有希望的替代方案.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 药物发现 药物发现 药物发现
背景情况:
- 化向化体 (PROTACs) 是向蛋白质降解 (TPD) 的一个突破.
- 由于蛋白质酶的约束,PROTACs仅限于细胞质蛋白质,并与聚合或膜结合的点作斗争.
- 蛋白质酶的局限性排除了许多与疾病相关的蛋白质,需要替代的降解途径.
研究的目的:
- 审查新兴的 lysosome-engaging TPD 策略领域.
- 探索基于 lysosome 的降解如何克服 PROTAC 的局限性.
- 评估 lysosome-engaging TPD 对各种治疗点的潜力.
主要方法:
- 目前关于 lysosome-engaging TPD 的文献综述.
- 对色素向降解剂的设计原则的分析.
- 案例研究评估成功的溶酶体参与TPD应用程序.
主要成果:
- 溶酶体可以降解广泛的宏分子和细胞结构,为蛋白质体降解提供了替代方案.
- 溶酶体参与的TPD策略有效地准了PROTAC无法访问的蛋白质,包括膜和细胞外蛋白质.
- 成功的案例研究证明了溶酶体参与TPD对各种具有挑战性的点的潜力.
结论:
- 溶酶体参与的TPD使向蛋白质降解工具包多样化.
- 这种方法克服了PROTAC的关键局限性,扩大了TPD的范围.
- lysosome-engaging TPD 在治疗更广泛的人类疾病方面具有重大前景.
相关概念视频
01:13The Proteasome
1.9K
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...
1.9K
02:18The Proteasome
10.4K
Eukaryotic cells can degrade proteins through several pathways. One of the most important amongst 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. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
10.4K
02:18The Proteasome
4.9K
4.9K
02:58Regulated Protein Degradation
9.1K
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...
9.1K
02:58Regulated Protein Degradation
3.3K
3.3K
01:36Delivery Pathways to the Lysosome
10.4K
Eukaryotic cells use different mechanisms to eliminate toxic waste obsolete and worn-out substances. Lysosomes play a pivotal role in this, and hence, these substances are carried to the lysosome from other parts of the cell and extracellular space through different pathways. The most elaborately studied pathways to the lysosome are the endocytic pathways.
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
10.4K