纳米体疗法挽救了NMDA受体低功能的行为缺陷
Mathieu Oosterlaken1, Angelina Rogliardo1,2, Tatiana Lipina3
1Institut de Génomique Fonctionnelle, Université de Montpellier, CNRS, INSERM, Montpellier, France.
Nature
|July 23, 2025
概括
研究人员开发了一种新的纳米体疗法, 能够成功地准大脑受体, 并纠正小鼠模型中的认知缺陷. 这一突破为治疗精神病和神经退行性疾病提供了有前途的新途径.
科学领域:
- 神经科学
- 免疫疗法
- 药物开发
背景情况:
- 精神病和神经退行性疾病需要新的治疗方法.
- 传统的免疫疗法在透大脑方面面临挑战.
- 卡梅利德重链抗体 (纳米体) 具有针对大脑的潜力.
研究的目的:
- 开发和评估针对大脑受体的双价双类纳米体.
- 评估纳米体对认知缺陷的治疗潜力.
- 建立纳米体作为治疗大脑疾病的可行策略.
主要方法:
- 使用两种驼类重链纳米体开发一种双价双类抗体.
- 一个纳米体与甲基胺受体2结合,另一个增强其活性.
- 在临床前小鼠模型中外接纳纳米体.
主要成果:
- 这种双价纳米体在外周给药后成功进入大脑.
- 在NMDA受体低功能的小鼠模型中纠正了认知缺陷.
- 在一次注射后,治疗效果持续至少7天,并且在次慢性治疗中保持.
结论:
- 纳米体可以有效地针对大脑的受体进行治疗.
- 这项研究为基于纳米体的脑疗法提供了概念证明.
- 这些发现为治疗精神和神经退行性疾病等大脑疾病提供了新的可能性.
相关概念视频
Ligand-gated Ion Channels
Ligand-gated ion channels are transmembrane proteins with a channel for ions to pass through and a binding site for a ligand. The channel opens only when a ligand attaches to the binding site.
Three Subfamilies of Ligand-gated Ion Channels
Ligand-gated ion channels fall into three subfamilies. The 'Cys-loop' includes the nicotinic acetylcholine receptors, γ-aminobutyric acid (GABA), glycine, and 5-hydroxytryptamine receptors. The second one is the 'Pore-loop' channels that include the...
Three Subfamilies of Ligand-gated Ion Channels
Ligand-gated ion channels fall into three subfamilies. The 'Cys-loop' includes the nicotinic acetylcholine receptors, γ-aminobutyric acid (GABA), glycine, and 5-hydroxytryptamine receptors. The second one is the 'Pore-loop' channels that include the...
Ligand-Gated Ion Channel Receptor: Gating Mechanism
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...
Neurochemical Transmission: Sites of Drug Action
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...
Nondepolarizing (Competitive) Neuromuscular Blockers: Mechanism of Action
Nondepolarizing neuromuscular blockers induce paralysis by competitively blocking nicotinic acetylcholine receptors at the muscle end plate. Examples include pancuronium, mivacurium, vecuronium, and rocuronium. These quaternary ammonium derivatives are administered intravenously, are poorly absorbed, and are excreted via the kidneys.
Competitive antagonists prevent acetylcholine from binding to its receptor, inhibiting membrane depolarization. Without conformational changes or intrinsic...
Competitive antagonists prevent acetylcholine from binding to its receptor, inhibiting membrane depolarization. Without conformational changes or intrinsic...
Cognitive Enhancers: Cholinesterase Inhibitors and NMDA Receptor Antagonists
Cognitive enhancers, also known as "smart drugs," are substances used to enhance memory, mental alertness, and concentration. These can be natural or synthetic and improve cognition in conditions like Alzheimer's disease (AD) and other neurodegenerative diseases. Some common examples include caffeine, amphetamines, methylphenidate, modafinil, arecoline, donepezil, vortioxetine, and piracetam. These enhancers work on the principle of synaptic plasticity and altered circuit function. They...
Alzheimer's Disease: Treatment
Alzheimer's Disease (AD), a neurodegenerative disorder, is pathologically identified by amyloid plaques and neurofibrillary tangles composed of tau protein. AD pharmacotherapy aims to manage cognitive symptoms, delay disease progression, and treat behavioral symptoms. The treatment is primarily symptomatic and palliative, with no definitive disease-modifying therapy available. Cholinesterase inhibitors, including donepezil (Aricept), rivastigmine (Exelon), and galantamine (Razadyne), are...


