工程制造的环氧化物阻断神经元刺激毒性
Daryl Ariawan1, Julia van der Hoven1, Nicolle Morey1
1Dementia Research Centre, Macquarie Medical School, Macquarie University 2109 Sydney, Australia.
Journal of medicinal chemistry
|December 4, 2024
概括
修改后的带有聚氨的环氧化物有效地将治疗性分泌到神经细胞中,防止刺激毒性并减少小鼠的发作严重程度. 这种方法可以增强神经系统疾病的神经保护.
科学领域:
- 生物化学 生物化学
- 神经科学是一个神经科学.
- 类治疗药物 类治疗药物
背景情况:
- 循环是一种稳定的循环,具有潜在的治疗应用.
- 通过后突触密度蛋白95和NMDA受体 (NMDARs) 介导的兴奋毒性,有助于神经系统疾病中的神经元细胞死亡.
- 有效的细胞内输送治疗性质到神经元仍然是一个挑战.
研究的目的:
- 为了增强治疗性的细胞内传递,使用修改后的环酸骨干.
- 开发一种针对PSD-95/NMDAR相互作用的新型神经保护剂.
- 评估修改后的循环在预防兴奋毒性和发作方面的疗效.
主要方法:
- 为了改善细胞吸收,MCoTI-II环氧化物被修改为聚氨酸骨干.
- 一个PSD-95/NMDAR抑制剂序列 (NR2B9c) 被移植到循环的循环6.
- 在体外研究中,使用N-甲基-D-酸盐 (NMDA) 和c5R-NR2B9c环氧化物治疗的初级神经元.
- 在体内研究中,在小鼠中使用了化学诱导的发作模型.
主要成果:
- 聚氨酸修饰显著增强了环类的吸收到神经元细胞.
- 经NR2B9c修饰的cyclotide (c5R-NR2B9c) 保护了主要神经元免受NMDA诱导的兴奋毒性.
- 在小鼠中使用c5R-NR2B9c增加了生存率,并降低了发作的严重程度.
- 该研究表明,通过增强的递送,通过激发性毒性进行了成功的神经保护.
结论:
- 聚氨酸修饰的环氧化物作为有效的载体,为治疗性的细胞内传递到神经元.
- 这一策略为开发由兴奋毒性为特征的神经系统疾病的治疗方法提供了一个有前途的方法.
- 该c5R-NR2B9c环氧化物显示出作为神经保护治疗剂的潜力.
相关概念视频
Ligand-Gated Ion Channel Receptor: Gating Mechanism
2.1K
Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
2.1K
Depolarizing Blockers: Mechanism of Action
1.4K
Depolarizing blockers act on skeletal muscle fibers' membranes and induce their depolarization. Most depolarizing blockers have two quaternary N+ atoms that bind the nicotinic acetylcholine receptors and cause neuromuscular blockade within minutes.
Succinylcholine is the most commonly used depolarizing blocker. Chemically, it constitutes two molecules of acetylcholine joined together by an acetate methyl group. They act on the receptors in the same way as acetylcholine. Because...
Succinylcholine is the most commonly used depolarizing blocker. Chemically, it constitutes two molecules of acetylcholine joined together by an acetate methyl group. They act on the receptors in the same way as acetylcholine. Because...
1.4K
Drugs Affecting Neurotransmitter Synthesis
1.3K
Drugs affecting neurotransmitter synthesis can impact the adrenergic neuron and the synthesis of neurotransmitters. For example, α-methyltyrosine and carbidopa target specific enzymes involved in catecholamine synthesis. α-methyltyrosine inhibits the enzyme tyrosine hydroxylase, which converts tyrosine into dopamine. By blocking this enzyme, α-methyltyrosine reduces dopamine production and other catecholamines. Carbidopa, on the other hand, inhibits the enzyme dopa decarboxylase,...
1.3K
Antiepileptic Drugs: Glutamate Antagonists
281
Glutamate is a fundamental neurotransmitter in the central nervous system, playing a vital role in neuronal communication and various cognitive processes. Glutamate stands as the principal excitatory neurotransmitter in the brain. Its presence is crucial for the communication between neurons, underpinning essential processes such as synaptic transmission, neuronal excitability, and plasticity. These functions are vital for higher-order cognitive processes, including learning and memory. The...
281
Neurochemical Transmission: Sites of Drug Action
2.1K
Neurochemical transmission, the conduction of electrical impulses between neurons mediated by neurotransmitters, plays a vital role in various physiological processes. Autonomic drugs exert their effects by modulating neurotransmission within the autonomic nervous system. For instance, drugs such as hemicholinium block the precursor uptake necessary for synthesizing acetylcholine, an essential autonomic neurotransmitter. Following synthesis, neurotransmitters are stored in vesicles. Metyrosine...
2.1K
Depolarizing Blockers: Pharmocokinetics
305
Depolarizing blockers are administered through intravenous injection. Succinylcholine is the most common choice of depolarizing blockers in emergency clinical practices. Although they have a rapid onset, they readily diffuse away from the motor end plate into the extracellular fluid. They are metabolized by enzymes such as liver butyrylcholinesterase and plasma pseudocholinesterases. This produces a short duration of action, typically 5-10 minutes long, unlike nondepolarizing blockers, which...
305


