Pathophysiological basis in the management of myasthenia gravis: a mini review

Binu, Aiswarya; Kumar, Sarath S.; Devi, P. Uma; Madhu, Krishnadas

doi:10.1007/s10787-021-00905-9

Cited by 5 publications

(2 citation statements)

References 49 publications

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“…Anti-ACHR antibodies are identified as the leading cause of MG in 80%–90% of the diagnosed patients [ 36 ]. Reports revealed that SS decreased ACHR-ab levels in EAMG rats [ 9 ].…”

Section: Discussionmentioning

confidence: 99%

Study on the Potential Mechanism of Semen Strychni against Myasthenia Gravis Based on Network Pharmacology and Molecular Docking with Experimental Verification

Fang

Liu

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Background. Semen Strychni (SS) is an effective Chinese medicine formula for treating myasthenia gravis (MG) in clinics. Nonetheless, its molecular mechanism is largely unknown. Objective. Using network pharmacology, molecular docking, and experimental validation, we aim to identify the therapeutic effect of SS on MG and its underlying mechanism. Methods. The main ingredients of SS and their targets and potential disease targets for MG were extracted from public databases. The protein-protein interaction (PPI) network was constructed using the STRING 11.0 database, and Cytoscape was used to identify the hub targets. In addition, Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to identify molecular biological processes and signaling pathways. Then, AutoDock Via conducted molecular docking. The experimental autoimmune myasthenia gravis (EAMG) model in female Lewis rats, quantitative real-time polymerase chain reaction (qRT-PCR), Western blot, and enzyme-linked immunosorbent assay (ELISA) were performed to confirm the effect and mechanism of SS on MG. Results. The following active compounds and hub targets were identified by screening and analyzing: isobrucine, vomicine, (S)-stylopine, strychnine, brucine-N-oxide, brucine and AKT1, MAPK1, MAPK14, CHRM1, ACHE, and CHRNA4. KEGG enrichment analyses indicated that the cholinergic synapse and neuroactive ligand-receptor interaction signaling pathway may be necessary. The results of molecular docking revealed that the main active ingredients bind well to the hub targets. In vivo experiments proved that SS could improve the weight loss and Lennon scores in the EAMG model. Experiments in molecular biology showed that SS could treat MG by affecting the cholinergic synapse through the respective antibody, receptor, and key enzymes in the cholinergic pathway. Conclusion. This study provided a preliminary overview of the active constituents, primary targets, and potential pathways of SS against MG. SS ameliorated EAMG by regulating the cholinergic synaptic junction.

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“…Anti-ACHR antibodies are identified as the leading cause of MG in 80%–90% of the diagnosed patients [ 36 ]. Reports revealed that SS decreased ACHR-ab levels in EAMG rats [ 9 ].…”

Section: Discussionmentioning

confidence: 99%

Study on the Potential Mechanism of Semen Strychni against Myasthenia Gravis Based on Network Pharmacology and Molecular Docking with Experimental Verification

Fang

Liu

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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“…In the central nervous system, it is involved in growth, development, and aging-regulating neural plasticity, differentiation, proliferation, and clearance of aged neurons . It is also involved in a large variety of pathophysiological conditions, such as different myasthenic syndromes, myasthenia gravis, in particular, Alzheimer’s disease (AD), the most prevalent neurodegenerative disorder in the elderly characterized by progressive cognitive decline, Tourette syndrome, and nocturnal frontal lobe epilepsies, among others. − Although the occurrence of these different pathophysiological conditions is due to different causes–multifactorial events in some cases–from a therapeutic point of view, they can be classified into two main groups. One group includes the first two above-mentioned pathological conditions, among others, sharing the “cholinergic hypothesis” that is related to a deficit of functional nAChR, and hence nAChR function potentiation is the therapeutic goal (muscle nAChR in the case of myasthenic syndromes and neuronal nAChR for AD, becoming α7 nAChR increasingly more important for AD pathology).…”

Section: Introductionmentioning

confidence: 99%

New Multitarget Molecules Derived from Caffeine as Potentiators of the Cholinergic System

Munafó,

Biscussi,

Obiol

et al. 2024

ACS Chem. Neurosci.

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Cholinergic deficit is a characteristic factor of several pathologies, such as myasthenia gravis, some types of congenital myasthenic syndromes, and Alzheimer's Disease. Two molecular targets for its treatment are acetylcholinesterase (AChE) and nicotinic acetylcholine receptor (nAChR). In previous studies, we found that caffeine behaves as a partial nAChR agonist and confirmed that it inhibits AChE. Here, we present new bifunctional caffeine derivatives consisting of a theophylline ring connected to amino groups by different linkers. All of them were more potent AChE inhibitors than caffeine. Furthermore, although some of them also activated muscle nAChR as partial agonists, not all of them stabilized nAChR in its desensitized conformation. To understand the molecular mechanism underlying these results, we performed docking studies on AChE and nAChR. The nAChR agonist behavior of the compounds depends on their accessory group, whereas their ability to stabilize the receptor in a desensitized state depends on the interactions of the linker at the binding site. Our results show that the new compounds can inhibit AChE and activate nAChR with greater potency than caffeine and provide further information on the modulation mechanisms of pharmacological targets for the design of novel therapeutic interventions in cholinergic deficit.

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Saliva

Mandel

2024

Clinical Management of Salivary Gland Disorders

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Pathophysiological basis in the management of myasthenia gravis: a mini review

Cited by 5 publications

References 49 publications

Study on the Potential Mechanism of Semen Strychni against Myasthenia Gravis Based on Network Pharmacology and Molecular Docking with Experimental Verification

Study on the Potential Mechanism of Semen Strychni against Myasthenia Gravis Based on Network Pharmacology and Molecular Docking with Experimental Verification

New Multitarget Molecules Derived from Caffeine as Potentiators of the Cholinergic System

Saliva

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