针对神经退行性疾病中的线粒细胞衰变
Odetta Antico1,2, Paul W Thompson3, Nicholas T Hertz4
1MRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee, UK.
Nature reviews. Drug discovery
|January 14, 2025
概括
增强细胞清洁过程 - - 线粒细胞吸收 - - 对治疗像帕金森氏症和阿尔茨海默氏症这样的神经退行性疾病有前途. 针对线粒细胞衰减的治疗方法现在正在进入临床试验.
科学领域:
- 神经科学是一个神经科学.
- 细胞生物学 细胞生物学
- 遗传学 遗传学 是一个
背景情况:
- 线粒体功能障碍是神经退行性疾病的关键特征,如帕金森病 (PD),肌缩侧面硬化症 (ALS),阿尔茨海默病 (AD) 和亨廷顿病 (HD).
- 与家族性PD和ALS相关的遗传突变往往会损害细胞,这是一个关键的细胞过程,用于去除受损的线粒体.
研究的目的:
- 探索增强神经退行性疾病的线粒细胞衰变途径的治疗潜力.
- 为了强调在这些条件下对神经保护和疾病修饰的未满足需求.
主要方法:
- 对基因,分子和临床前证据的审查,这些证据支持线粒增强.
- 识别小分子线性增强剂,包括USP30抑制剂和PINK1激活剂.
主要成果:
- 强有力的证据支持将食细胞作为神经退行性疾病的治疗策略.
- 选择性线粒细胞增强的小分子方法正在取得进展.
结论:
- 增强线粒能通过解决潜在的致病机制,为神经退行性疾病提供了一条新的治疗途径.
- USP30抑制剂和PINK1激活剂正在进入I期临床试验,这代表了向前迈出的重要一步.
相关概念视频
Electron Transport Chain: Complex I and II
10.9K
The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
ROS generation is regulated and maintained at moderate levels necessary...
10.9K
Autophagy
4.2K
Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
4.2K
Translocation of Proteins into the Mitochondria
3.0K
Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
3.0K
Delivery Pathways to the Lysosome
6.1K
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...
6.1K
Autophagic Cell Death
3.3K
Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
3.3K
The Proteasome
807
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...
807


