人类单克隆抗体对B型肉毒神经毒素的中和机制
Takuhiro Matsumura1, Mayu Kitamura1, Sho Amatsu1
1Department of Bacteriology, Graduate School of Medical Sciences, Kanazawa University, Ishikawa, Japan.
Microbiology and immunology
|September 6, 2024
概括
两个新的人类单克隆抗体M2和M4可以中和B型肉毒神经毒素 (BoNT/B). 它们通过不同的机制一起工作,抑制BoNT/B结合和转位,为先进的肉毒治疗铺平了道路.
科学领域:
- 神经科学是一个神经科学.
- 免疫学 免疫学 免疫学
- 微生物学 微生物学
背景情况:
- 肉毒是一种严重的神经麻性疾病,由肉毒神经毒素 (BoNTs) 引起.
- 毒素中和抗体对于治疗肉毒毒素中毒至关重要.
- 开发针对BoNTs的有效治疗抗体是一个持续的挑战.
研究的目的:
- 描述两种新型人类单克隆抗体M2和M4对B型肉毒神经毒素 (BoNT/B) 的作用机制.
- 调查结合M2和M4抗体对BoNT/B.的协同中和作用.
- 探索开发针对肉毒的先进抗体治疗方法的潜力.
主要方法:
- 产生针对BoNT/B.的人类单克隆抗体M2和M4.
- 抗体机制的体外分析,包括结合试验和使用PC12细胞的基于细胞的试验.
- 评估BoNT/B与神经元细胞的结合和基质裂解抑制.
主要成果:
- M4抗体通过向重链的受体结合域来抑制BoNT/B与神经元PC12细胞的结合.
- M2抗体向轻链,但不抑制基质裂变;它似乎抑制L链转位.
- 结合的M2和M4抗体显示出对BoNT/B毒性的强有力的协同中和作用.
结论:
- M2和M4抗体具有不同的作用机制,单独针对BoNT/B中毒的不同阶段.
- 抗体组合的多步抑制是它们协同治疗效果的关键.
- 这些发现支持开发有效的合抗体疗法治疗肉毒主义.
相关概念视频
Directly Acting Muscle Relaxants: Dantrolene and Botulinum Toxin
661
Directly acting muscle relaxants like dantrolene and botulinum toxin (BoNT) have distinct mechanisms and applications. Dantrolene, a hydantoin derivative, acts on the ryanodine receptor (RYR1) in skeletal muscle cells. RYR1 are calcium channels present at the sarcoplasmic reticulum membrane. In response to excitation, they release calcium ions from the sarcoplasmic reticulum to the cytosol. Calcium promotes actin-myosin-mediated contraction of muscles.
The binding of dantrolene to the RYR1...
The binding of dantrolene to the RYR1...
661
Nondepolarizing (Competitive) Neuromuscular Blockers: Mechanism of Action
1.7K
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...
1.7K
Nondepolarizing (Competitive) Neuromuscular Blockers: Pharmacological Actions
401
Nondepolarizing neuromuscular blockers prevent the membrane depolarization of muscle cells and inhibit muscle contraction. These are usually administered with anesthetics to achieve complete muscle relaxation. Upon administration, these drugs first block the small, rapidly contracting muscles of the face and hands, followed by the larger muscles of the trunk and the intercostal muscles. The diaphragm is the last muscle to be affected.
Although all competitive neuromuscular blockers are designed...
Although all competitive neuromuscular blockers are designed...
401
Antibody Actions
1.1K
Antibodies, or immunoglobulins, are critical players in the immune system's arsenal against invading pathogens. Produced by B cells and plasma cells, their primary role is to detect and bind to specific antigens, molecules found on the surface of pathogens like bacteria or viruses. Beyond antigen recognition, antibodies perform several vital functions that contribute to immune defense.
Neutralization
Antibodies can bind to pathogens, preventing them from infecting host cells. This process...
Neutralization
Antibodies can bind to pathogens, preventing them from infecting host cells. This process...
1.1K
Humoral Immune Responses
72.3K
Overview
72.3K
Hybridoma Technology
14.2K
Hybridoma technology is used for the large-scale production of monoclonal antibodies. Monoclonal antibodies bind to only a single antigenic determinant or epitope. Such antibodies are used in research, diagnostics, and disease therapy. The hybridoma technology established in 1975 by Georges Köhler and Cesar Milstein was awarded the Nobel Prize in Medicine in 1984 for revolutionizing research and therapy.
Hybridoma Selection
Commonly used fusion techniques — electroporation,...
Hybridoma Selection
Commonly used fusion techniques — electroporation,...
14.2K


