Congenital myasthenic syndromes with acetylcholinesterase deficiency, the pathophysiological mechanisms

Legay, Claire

doi:10.1111/nyas.13595

Cited by 16 publications

(11 citation statements)

References 51 publications

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“…Neuroactive ligand-receptor interaction [24] , endocrine regulated calcium reabsorption [25] , cholinergic synapse [26] , Hedgehog signaling pathway [27] are mainly related to the inflammatory reaction and the occurrence and development of cancer cells and participates in the process of cell cycle change and apoptosis. TGF-β signaling pathway [28] can affect PTGS2 -and ADRB2 gene to mediate brain activity, thus affecting the transmission of neural information.…”

Section: Resultsmentioning

confidence: 99%

Network Pharmacological Study of Yiyi-Fuzi-Baijiang powder in Treating Colorectal Cancer

Wang¹,

Sun²,

Lu³

et al. 2020

pharmaceutical-sciences

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Wang et al.: Pharmacological Study of Yiyi-Fuzi-Baijiang powder This investigation dealt with the analysis of the active ingredients of Yiyi-Fuzi-Baijiang powder in the treatment of colorectal cancer using computer network pharmacology technology to predict the mechanism of action. The chemical constituents and targets of Yiyi-Fuzi-Baijiang powder were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and the common targets in the treatment of colorectal cancer were obtained from Online Mendelian Inheritance in Man, Therapeutic Target Database and PharmGkb database. Excel was used to screen the molecular target and Cytoscape software was used to establish the network of Chinese medicine components target of Yiyi-Fuzi-Baijiang powder. The gene function and metabolic pathway were analyzed using the biological information annotation database. Nineteen components of Yiyi-Fuzi-Baijiang powder were found to interact with 121 target proteins of colorectal cancer, including progesterone receptor, prostaglandin G/H synthase 2, gamma-aminobutyric acid receptor subunit alpha-1, prostaglandin G/H synthase 1, nuclear receptor co-activator 2, beta-2 adrenergic receptor, sodium channel protein type 5 subunit alpha, alpha-1B adrenergic receptor. It is the target of Chaihushugansan in the treatment of post-stroke depression, mainly involving in neuroactive ligand-receptor interaction, endocrine regulated calcium reabsorption, TGF-β signaling pathway, Hedgehog signaling pathway, inflammatory mediator regulation transient receptor potential channels, cholinergic synapse, through the regulation of the nervous system, cell cycle, apoptosis, inflammatory regulation, cell communication and other biological processes to treat colorectal cancer. The possible mechanism of Yiyi-Fuzi-Baijiang powder in treating colorectal cancer was revealed by network pharmacological study, which laid a foundation for further elucidation of its action target.

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Section: Resultsmentioning

confidence: 99%

Network Pharmacological Study of Yiyi-Fuzi-Baijiang powder in Treating Colorectal Cancer

Wang¹,

Sun²,

Lu³

et al. 2020

pharmaceutical-sciences

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“…Mutations in the central collagen domain containing two heparan sulfate proteoglycan binding (HSPBP) domains cause loss of assembly of the COLQ strands in a triple helix, and mutations in the C-terminal region lead to the synthesis of single-or triple-strands of COLQ-AChE, which are unable to bind to the basal lamina [3,9,12,33]. causative COLQ mutations cause an endplate AChE deficiency with an abnormality that varies from normal secretion with decreased activity to the total absence of the protein [25,26]. They are responsible for a broad range of severity and clinical features (from mild muscle weakness to wheelchair boundness, or early death) for congenital myasthenic syndrome type-5 [27,28].…”

Section: Fig 4 Venn Diagram Showing Possible Genes With Their Differe...mentioning

confidence: 99%

Novel copy number variation of COLQ gene in a Moroccan patient with congenital myasthenic syndrome: a case report and review of the literature

et al. 2022

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Background Congenital myasthenic syndromes (CMSs) are rare genetic diseases due to abnormalities of the neuromuscular junction leading to permanent or transient muscle fatigability and weakness. To date, 32 genes were found to be involved in CMSs with autosomal dominant and/or recessive inheritance patterns. CMS with acetylcholinesterase deficiency, in particular, was determined to be due to biallelic mutations of COLQ gene with early-onset clinical signs. Here, we report clinical features and novel molecular findings of COLQ-related CMS in a Moroccan patient with a review of the literature for this rare form. Case presentation In this study, we report the case of a 28-month-old Moroccan female patient with hypotonia, associated to axial muscle weakness, global motor delay, bilateral ptosis, unilateral partial visual field deficiency with normal ocular motility, and fatigable muscle weakness. Clinical exome sequencing revealed a novel homozygous deletion of exon 13 in COLQ gene, NM_005677.4(COLQ):c.(814+1_815-1)_(954+1_955-1) del p.(Gly272Aspfs*11). This finding was subsequently confirmed by quantitative real-time PCR (qPCR) in the proband and her parents. In silico analysis of protein-protein interaction network by STRING tool revealed that 12 proteins are highly associated to COLQ with an elevated confidence score. Treatment with Salbutamol resulted in clear benefits and recovery. Conclusions This clinical observation illustrates the important place of next-generation sequencing in the precise molecular diagnosis of heterogeneous forms of CMS, the appropriate management and targeted treatment, and genetic counseling of families, with a better characterization of the mutational profile of this rare disease in the Moroccan population.

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“…First, the prolonged time of ACh at the synaptic cleft produce desensitization of AChRs and secondary endplate myopathy with loss of AChRs due to sarcoplasmic Ca 2+ overload [ 51 ]. Second, if COLQ mutations alter the interaction of ColQ with MuSK or perlecan, this could impact postsynaptic differentiation [ 52 , 53 ]. COLQ mutations have been reported in all domains of the protein with no phenotype–genotype correlation [ 54 ].…”

Section: Synaptic and Basal-lamina Associated Syndromesmentioning

confidence: 99%

The Neuromuscular Junction and Wide Heterogeneity of Congenital Myasthenic Syndromes

Cruz

Palace

Beeson

2018

IJMS

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Congenital myasthenic syndromes (CMS) are genetic disorders characterised by impaired neuromuscular transmission. This review provides an overview on CMS and highlights recent advances in the field, including novel CMS causative genes and improved therapeutic strategies. CMS due to mutations in SLC5A7 and SLC18A3, impairing the synthesis and recycling of acetylcholine, have recently been described. In addition, a novel group of CMS due to mutations in SNAP25B, SYT2, VAMP1, and UNC13A1 encoding molecules implicated in synaptic vesicles exocytosis has been characterised. The increasing number of presynaptic CMS exhibiting CNS manifestations along with neuromuscular weakness demonstrate that the myasthenia can be only a small part of a much more extensive disease phenotype. Moreover, the spectrum of glycosylation abnormalities has been increased with the report that GMPPB mutations can cause CMS, thus bridging myasthenic disorders with dystroglycanopathies. Finally, the discovery of COL13A1 mutations and laminin α5 deficiency has helped to draw attention to the role of extracellular matrix proteins for the formation and maintenance of muscle endplates. The benefit of β2-adrenergic agonists alone or combined with pyridostigmine or 3,4-Dyaminopiridine is increasingly being reported for different subtypes of CMS including AChR-deficiency and glycosylation abnormalities, thus expanding the therapeutic repertoire available.

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Congenital myasthenic syndromes with acetylcholinesterase deficiency, the pathophysiological mechanisms

Cited by 16 publications

References 51 publications

Network Pharmacological Study of Yiyi-Fuzi-Baijiang powder in Treating Colorectal Cancer

Network Pharmacological Study of Yiyi-Fuzi-Baijiang powder in Treating Colorectal Cancer

Novel copy number variation of COLQ gene in a Moroccan patient with congenital myasthenic syndrome: a case report and review of the literature

The Neuromuscular Junction and Wide Heterogeneity of Congenital Myasthenic Syndromes

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