LONRF2是一种蛋白质质量控制的基因酶,其缺乏导致晚期发作的神经缺陷
Dan Li1, Yoshikazu Johmura2,3, Satoru Morimoto4
1Division of Cancer Cell Biology, The University of Tokyo, Tokyo, Japan.
Nature aging
|July 20, 2023
概括
研究人员发现,蛋白质质量控制链酶LONRF2对于神经元健康至关重要. 它的损失导致运动神经元退化,这表明像ALS这样的神经退行性疾病的新目标.
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
- 分子生物学分子生物学
背景情况:
- 蛋白质错误折叠是神经退行性疾病的关键驱动因素.
- 转移后的神经元由于缺乏细胞分裂,容易受到蛋白质聚合物的影响.
- 在转移后的细胞中可能存在特定的蛋白质质量控制系统.
研究的目的:
- 识别和表征一个蛋白质质量控制系统在后转移神经元.
- 调查LONRF2在神经元蛋白质稳态和神经退行症中的作用.
主要方法:
- 研究了老化的细胞和神经元中的LONRF2表达和功能.
- 评估了LONRF2对错误折叠的蛋白质的结合和无处不在 (TDP-43, hnRNP M1).
- 分析了Lonrf2淘汰赛小鼠和患者衍生的运动神经元 (MN).
主要成果:
- 确定LONRF2是一种在衰老细胞中诱导的,主要在神经元中表达的泛素酶.
- LONRF2的目标是异常结构的TDP-43, hnRNP M1和错误折叠的蛋白质.
- 在小鼠中,Lonrf2 缺乏导致了年龄相关的运动神经元退化和动力衰竭.
- 干细胞衍生的MNs中LONRF2的丧失导致生存率降低,神经元缩短和蛋白质聚合.
- 宫外LONRF2表达在患者衍生的ALS MNs中挽救了神经元缩短.
结论:
- LONRF2是神经元中一个关键的蛋白质质量控制链酶.
- 失去LONRF2功能有助于运动神经元退化和运动缺陷.
- LONRF2代表了神经退行性疾病的潜在治疗标.
相关概念视频
01:29Protein Folding Quality Check in the RER
3.8K
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...
3.8K
01:37Neural Regulation
39.6K
Digestion begins with a cephalic phase that prepares the digestive system to receive food. When our brain processes visual or olfactory information about food, it triggers impulses in the cranial nerves innervating the salivary glands and stomach to prepare for food.
39.6K
02:39lncRNA - Long Non-coding RNAs
8.7K
In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA...
8.7K
01:03Long-term Depression
2.6K
Long-term depression, or LTD, is one of the ways by which synaptic plasticity—changes in the strength of chemical synapses—can occur in the brain. LTD is the process of synaptic weakening that occurs over time between pre and postsynaptic neuronal connections. The synaptic weakening of LTD works in opposition to synaptic strengthening by long-term potentiation (LTP) and together are the main mechanisms that underlie learning and memory.
Calcium Ion Concentration Mechanism
If over...
Calcium Ion Concentration Mechanism
If over...
2.6K
01:22Lysosomal Hydrolases
3.8K
Lysosomes are the site for the degradation of macromolecules and biological polymers released during membrane trafficking events such as secretory, endocytic, autophagic, and phagocytic pathways. The membrane-enclosed area of the lysosome, called the lumen, contains hydrolytic enzymes active in an acidic environment. These acid hydrolases are functional at a pH between 4.5 and 5 and are involved in cellular processes such as cell signaling, energy metabolism, restoration of the plasma membrane,...
3.8K
01:31Translation
15.0K
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of Life
Proteins are...
Translation Produces the Building Blocks of Life
Proteins are...
15.0K