相关实验视频

Updated: Jun 4, 2025

Characterization of Neuronal Lysosome Interactome with Proximity Labeling Proteomics

Characterization of Neuronal Lysosome Interactome with Proximity Labeling Proteomics

Published on: June 23, 2022

Lysosome-Targeting 蛋白质降解通过内细胞化途径触发多价纳米奇米拉用于AD治疗的AD治疗

Xiaorong Wang¹, Shiqin Chen¹, Xue Xia¹

¹Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China.

Advanced materials (Deerfield Beach, Fla.)

|December 17, 2024

概括

一种新的纳米奇米拉 (endoTAC) 通过向溶酶体来增强阿尔茨海默病标记物RAGE的降解. 这个系统还精确地向大脑输送药物,扭转疾病病理.

科学领域:

生物医学工程生物医学工程
神经科学是一个神经科学.
药物输送系统药物输送系统

背景情况:

对于先进的糖化终产品 (RAGE) 的受体的升调是阿尔茨海默氏病发病的一个关键驱动因素.
lysosome-targeting 蛋白质降解显示了治疗潜力,但由于低效的 lysosome 分类而受到限制.
准RAGE是阿尔茨海默病治疗的有希望的策略.

研究的目的:

开发一种类似于 lysosome-shuttle 的纳米奇美拉 (endoTAC),用于增强 RAGE 降解.
评估endoTAC作为大脑精确药物输送系统的有效性.
为了研究将溶酶体向与阿尔茨海默病的药物输送相结合的治疗潜力.

主要方法:

一个纳米奇米拉 (endoTAC) 的设计,利用RAGE的多价受体结合模式.
在体外评估endoTAC的亲和力和RAGE降解增强.
在体内评估endoTAC的大脑积累和药物输送能力.
在endoTAC (SV@endoTAC) 上加载simvastatin并测试其治疗效果.

主要成果:

恩多塔克表现出对RAGE的高度亲和力,通过多价相互作用显著增强了其降解.
恩多塔克在患病的大脑组织中增加了积累,验证了其作为大脑输送系统的潜力.
在体外和体内阿尔茨海默氏症模型中,SV@endoTAC有效地逆转了病理特征.

结论:

开发的endoTAC纳米奇美拉有效地准并降解RAGE,这是阿尔茨海默氏症的一个关键标志物.
恩多塔克作为一个有前途的平台,精确的药物输送到大脑.
将 lysosome-targeting 策略与有效的药物输送系统相结合,为阿尔茨海默病提供了一种强大的治疗方法.

关键词:

阿尔茨海默病的疾病阿尔茨海默病的疾病.BBB维修公司溶酶体向蛋白质降解的降解纳米输送系统的纳米输送系统.多价结合剂多价结合剂

更多相关视频

Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?

Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?

Published on: June 13, 2014

High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines

High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines

Published on: November 9, 2020

相关概念视频

The Proteasome

The Proteasome

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...

Delivery Pathways to the Lysosome

Delivery Pathways to the Lysosome

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...

Export of Misfolded Proteins out of the ER

Export of Misfolded Proteins out of the ER

After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...

Lysosomal Hydrolases

Lysosomal Hydrolases

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,...

Receptor-mediated Endocytosis

Receptor-mediated Endocytosis

Recycling Endosomes and Transcytosis

Recycling Endosomes and Transcytosis

The recycling endosome, also known as the endosomal recycling compartment (ERC), is a part of the slow-recycling process of the endocytic pathway. Molecules internalized through receptor-mediated endocytosis are either degraded in the lysosomes or are recycled to the plasma membrane through the fast- or slow-recycling route.
The recycling endosome is not a single organelle but an extensively tubulated network of recycling pathways. It functions in storing molecules or transporting them across...