通过使用可激活的先导体策略来构建"智能"化剂,用于治疗威尔逊病
Chengcheng Wang1, Roumin Wang2, Lingzhou Zhao3
1State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Chemistry and Chemical Engineering, Donghua University, Shanghai, 201620, China.
Redox biology
|February 10, 2024
概括
这项研究引入了一种针对威尔逊病 (WD) 的新型预兆剂,该预兆剂针对肝脏中的铜 (Cu) 积累. 通过精确地输送Cu化剂,化器最大限度地减少了副作用,为WD患者提供了更安全的长期治疗.
科学领域:
- 生物化学 生化学
- 遗传学 遗传学 是一个
- 药理学 药理学是指药理学的学科.
背景情况:
- 威尔逊病 (WD) 是一种遗传性疾病,其特征是病态的铜 (Cu) 在肝脏中的积累.
- 目前的疗法涉及终身Cu化药物,由于非特异性的Cu排泄,往往会引起严重的副作用.
研究的目的:
- 在WD模型中开发一个用于精确和受控地将Cu化剂药物输送到肝脏的前器.
- 为了规避与传统WD治疗相关的有毒副作用.
主要方法:
- 构建一个设计用于向肝脏输送的新型前器.
- 通过反应性氧物种 (ROS) 激活生体,在WD肝脏中高度表达.
- 协同释放Cu化剂和甲基蓝 (MB) 以同时去除和监测Cu.
主要成果:
- 在WD肝模型中,在ROS激活时,前剂有效释放化剂和MB.
- 释放的化剂有效地与Cu协调,促进其从身体中去除.
- 治疗证明有效地抑制了WD病理进展.
结论:
- 开发的前器为威尔逊病提供了针对性和更安全的治疗策略.
- 这种创新方法通过将Cu化定位到肝脏来最大限度地减少系统性副作用.
- 生器有望改善威尔逊病的长期管理.
相关概念视频
Anticholinesterase Agents: Poisoning and Treatment
856
Anticholinesterases, also known as cholinesterase inhibitors, work by blocking the breakdown of acetylcholine, leading to its accumulation in the synaptic cleft. This accumulation indirectly enhances both muscarinic and nicotinic actions. These agents are classified as reversible or irreversible based on their mechanism of action.
Irreversible agents form a strong bond with the cholinesterase enzyme, making it inactive. The breakdown of the phosphorylated enzyme is...
Irreversible agents form a strong bond with the cholinesterase enzyme, making it inactive. The breakdown of the phosphorylated enzyme is...
856
Extraction: Advanced Methods
447
Metal ions can be separated from one another by complexation with organic ligands–the chelating agent– to form uncharged chelates. Here, the chelating agent must contain hydrophobic groups and behave as a weak acid, losing a proton to bind with the metal. Since most organic ligands used in this process are insoluble or undergo oxidation in the aqueous phase, the chelating agent is initially added to the organic phase and extracted into the aqueous phase. The metal-ligand complex is...
447
Masking and Demasking Agents
2.4K
EDTA titrations may necessitate masking and demasking agents to temporarily protect a particular metal ion in a mixture from the EDTA reaction. These agents facilitate the sequential analysis of the metal ions by forming stable complexes with some—but not all—metal ions during certain steps.
There are many masking agents, such as cyanide, fluoride, triethanolamine, thiourea, and 2,3-bis(sulfanyl)propan-1-ol (formerly 2,3-dimercapto-1-propanol), with the masking agent chosen based on...
There are many masking agents, such as cyanide, fluoride, triethanolamine, thiourea, and 2,3-bis(sulfanyl)propan-1-ol (formerly 2,3-dimercapto-1-propanol), with the masking agent chosen based on...
2.4K
Antidotes
644
Antidotes are medicinal substances used to counteract the harmful effects of toxins or drugs in the body. They function in various ways, each uniquely designed to combat specific toxic compounds.
Specific antidotes operate by inhibiting the enzymes that control biochemical pathways, reducing the production of harmful metabolites.
An example of an antidote is atropine, which counteracts the detrimental effects of cholinesterase inhibitors. It achieves this by deactivating muscarinic receptors,...
Specific antidotes operate by inhibiting the enzymes that control biochemical pathways, reducing the production of harmful metabolites.
An example of an antidote is atropine, which counteracts the detrimental effects of cholinesterase inhibitors. It achieves this by deactivating muscarinic receptors,...
644
Indirect-Acting Cholinergic Agonists: Mechanism of Action
1.8K
Indirect-acting cholinergic agonists work by interacting with an enzyme called acetylcholinesterase (AChE) in the synaptic cleft. They can be reversible or irreversible inhibitors and have different effects on the enzyme.
Reversible inhibitors like edrophonium bind to a specific part of the enzyme called the anionic catalytic site. They form noncovalent bonds, which means they are not strongly attached to the enzyme. This creates a temporary and less stable enzyme–inhibitor complex,...
Reversible inhibitors like edrophonium bind to a specific part of the enzyme called the anionic catalytic site. They form noncovalent bonds, which means they are not strongly attached to the enzyme. This creates a temporary and less stable enzyme–inhibitor complex,...
1.8K
Indirect-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship
565
Indirect-acting cholinergic agonists are agents that interact with the acetylcholinesterase enzyme in the synaptic cleft, preventing the breakdown of acetylcholine into choline and acetate. Consequently, the concentration of acetylcholine in the synaptic cleft increases. These agonists can be classified into reversible and irreversible inhibitors based on their duration of action.
Reversible inhibitors display short to medium durations of action. Short-acting agents include simple alcohols with...
Reversible inhibitors display short to medium durations of action. Short-acting agents include simple alcohols with...
565


