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Clinical Aspects
Published in Marc H. De Baets, Hans J.G.H. Oosterhuis, Myasthenia Gravis, 2019
An important finding was that anti-AChR antibodies from MG patients did not bind to the nicotinic AChR receptors extracted from human brain, nor did sera from patients with other neurological diseases, e.g., multiple sclerosis or Lambert-Eaton myasthenic syndrome. Additionally no binding of any of these sera to the alpha-bungarotoxin binding protein from human brain could be detected.131 Thus AChR in brain is antigenically distinct from the AChR in skeletal muscle, so that the low concentrations of anti-AChR antibodies in the cerebrospinal fluid do not bind to the AChRs in brain. The majority of these data, although not completely understood, confirm the clinical impression that in MG patients cerebral functions are normal, and not the target of an autoimmune process.
The Thymus and Immunotherapy, Reconstructive Vs. Stimulatory or Suppressive Conceptions
Published in Marek P. Dabrowski, Barbara K. Dabrowska-Bernstein, Immunoregulatory Role of Thymus, 2019
Marek P. Dabrowski, Barbara K. Dabrowska-Bernstein
Antoantibodies present in MG patients, directed to “A” bands of striated muscles, cross-react with thymic epithelial cells.338 Isolation of nicotinic acetylcholine (ACh) receptors and labeling these structures with the snake venom alpha-bungarotoxin,339 prompted the progress in the understanding of the pathogenesis of MG. In the majority of MG patients, B cells penetrate the thymus and form typical germinal centers synthesizing polyclonal immunoglobulins and anti-ACh receptor antibodies. In these patients, therapeutic thymectomy results in decreased levels of peripheral anti-ACh R antibodies and in corresponding improvement of neuromuscular transmission.340 In the group of remaining MG patients (10 to 20%), with developed thymoma, no clinical benefit is observed after thymectomy, suggesting the “peripheralization” of autoantibody production.
ENTRIES A–Z
Published in Philip Winn, Dictionary of Biological Psychology, 2003
Alpha-bungarotoxin is a POLYPEPTIDE which can bind irreversibly to NICOTINIC ACETYLCHOLINE RECEPTORS, where it acts as an ANTAGONIST. It has a powerful action at the NEUROMUSCULAR JUNCTION, which it blocks, leading to paralysis and death by asphyxiation. It has been extracted from the venom of the banded krait (Bungarus multicinctus), a very dangerous Taiwanese snake.
BNC210: an investigational α7-nicotinic acetylcholine receptor modulator for the treatment of anxiety disorders
Published in Expert Opinion on Investigational Drugs, 2023
Elliot Hampsey, Adam Perkins, Allan H. Young
BNC210 is a negative modulator of the α7 nAChR (see figure 1). BNC210 inhibits α7 nAChR currents in human cell lines with IC50 values in the range of 1.2 to 3 mM. It appears to act as a negative allosteric modulator, as it is neither displaced by alpha-bungarotoxin binding (a neurotoxin that competitively binds to nAChRs), nor are its effects impacted by the concentration of acetylcholine. There are no published data concerning BNC210ʹs off-target (i.e. non-nicotinic) activity. Data published by Wise, Patrick, & Meyer et al. [21], & Perkins, A., Patrick, F., Wise, T., et al. [22], suggest that the response to BNC210 may be hormetic, as low-dose, but not high dose, BNC210 resulted in reduced anxiolytic behaviors and reductions in scores on self-reported state anxiety.
In vitro models of neuromuscular junctions and their potential for novel drug discovery and development
Published in Expert Opinion on Drug Discovery, 2020
Olaia F Vila, Yihuai Qu, Gordana Vunjak-Novakovic
Alpha-bungarotoxin (BTX), a 74-amino acid polypeptide purified from the venom of the snake Bungarus multicinctus originally found in Taiwan [74], is another postsynaptic blocker frequently used to validate NMJ models. Santhanam et al. showed a dose-response curve to BTX treatment in their microfluidic NMJ system [46] whereas Uzel et al., and Vila et al. showed its ability to irreversibly stop both spontaneous and light-induced contractions in their mouse [60] and human [62] optogenetic NMJ models.