Involvement of activin a receptor type 1 (ACVR1) in the pathogenesis of primary focal hyperhidrosis

Lin, Jianbo; Chen, Jianfeng; Lai, Fan-Cai; Xu, Li; Xie, Jinbao; Tu, Yuan-rong; Kang, Myounggu

doi:10.1016/j.bbrc.2020.05.052

Cited by 11 publications

(9 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A pathogenesis study of PHH shows that the cholinergic receptor nicotinic alpha 1 subunit and activin a receptor type 1 maybe involvement of the pathogenesis of primary hyperhidrosis. [4,5] Another genomewide analysis of families with PHH shows that variants or mutations located outside the coding regions might be involved in the molecular pathogenesis of PHH. [3] In the Cox proportional hazard model for ineffective treatment show that higher risk in patients with family history than without, which the reason may from variants or mutations located outside the coding regions.…”

Section: Discussionmentioning

confidence: 99%

“…[1][2][3] which the cholinergic receptor nicotinic alpha 1 subunit and activin a receptor type 1 maybe involvement of the pathogenesis of primary hyperhidrosis. [4,5] The main involved symptom parts include hand, axilla, craniofacial region, and feet. [6,7] Hyperhidrosis causes great troubles to patients' social life and work, and even depression in severe cases; severely affected patients have skin maceration and secondary microbial infections.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Efficacy and Safety of Radiofrequency Ablation Versus Video-assisted Thoracoscopic Sympathectomy in Palmar Hyperhidrosis: A Multicenter Cohort Study

Zhong¹,

Zhu²,

Li³

et al. 2021

Preprint

View full text Add to dashboard Cite

Background: Radiofrequency ablation (RFA) was adopted as an alternative to surgical options for sympathectomy in patients with palmar hyperhidrosis (PHH), but the RFA comparative efficacy of treatments by video-assisted thoracoscopic sympathectomy (VATS) on long-term remains uncertain.Methods: We recruited patients aged ≥14 years with diagnosed PHH from 14 centers in China. The treatment options of RFA or VATS were recruited in patient with informed consent. The primary outcome was the clinical efficacy in 1-year. Propensity scoring and multivariable models respectively were used to evaluate the clinical efficacy and inefficacy risk of treatment options.Results: A total of 807 patients were enrolled, 351 patients underwent RFA, and 456 were VATS. After propensity score matching, the rate of complete remission was lower in RFA than in VATS (79.2% [247/312] versus 91.3% [285/312], 95% confidence intervals [CI] 0.21 to 0.57, p<0.001). However, the rate of palmar dryness (95% CI 0.38 to 0.92, p=0.020), of postoperative pain (95% CI 0.13 to 0.33, p<0.001), and of surgical-related complication (95% CI 0.19 to 0.85, p=0.020) is lower in RFA group than in VATS group, and radiofrequency ablation group of skin temperature rise is more common (95% CI 1.84 to 3.58, p<0.001).Conclusion: Performing RFA had a lower success rate than VATS for the complete remission of palmar hyperhidrosis. However, RFA may be better reasonable treatment option for palmar hyperhidrosis before surgical sympathectomy, because it more possibly accepted and generalized due to lower symptomatic burden and costs than surgical sympathectomy in patients.Trial RegistrationChiCTR2000039576, URL: http://www.chictr.org.cn/index.aspx

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Efficacy and Safety of Radiofrequency Ablation Versus Video-assisted Thoracoscopic Sympathectomy in Palmar Hyperhidrosis: A Multicenter Cohort Study

Zhong¹,

Zhu²,

Li³

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“… 8 , 9 The increase in the number of myelin nerve fibers and the thickening of myelin sheath are also one of its pathogeneses. Family genetic studies have shown that ACVR1 gene is overexpressed in sweat gland tissue of PFH patients, 10 and CHRNA1 gene is significantly upregulated in thoracic sympathetic ganglia. 11 Studies have shown that CHRNA1 is the cholinergic receptor nicotinic alpha1 subunit, which is involved in the binding and gating of the Ach neurotransmitter.…”

Section: Introductionmentioning

confidence: 99%

Antagonist of Chrna1 prevents the pathogenesis of primary focal hyperhidrosis

Lin

et al. 2022

Ann Clin Transl Neurol

Self Cite

View full text Add to dashboard Cite

Background: Primary focal hyperhidrosis (PFH) is an autonomic neurological disease in which exocrine glands are oversecreted due to autonomic dysfunction of the sympathetic nervous system. Chrna1 promotes the pathogenesis of PFH. We aimed to check if downregulating of Chrna1 by cisatracurium could alleviate the symptoms of PFH. Methods: The effect of cisatracurium in a hyperhidrosis mice model induced by pilocarpine hydrochloride was monitored for sweat gland secretion, and ultrastructural sweat secretory granules in sweat glands were analyzed. Meanwhile, markers of hyperhidrosis were checked, and release of Bdnf and Nrg1 from sympathetic ganglia axon was tested. Furthermore, the mechanism of cisatracurium function was evaluated in vitro using HEK293 expressing Chrna1. Finally, the effect of cisatracurium was determined in the hyperhidrosis mice model with overexpression or downregulation of Chrna1. Results: In hyperhidrosis mice, pretreatment with cisatracurium effectively inhibited sweat secretion, along with fewer particle secretion in sweat glands. The molecular markers of hyperhidrosis (Aqp5 and Cacna1c) were inhibited by cisatracurium, acetylcholine (Ach) level in serum was found decreased. Neurotrophic factors (Bdnf and Nrg1) secreted by sympathetic axon activation were also inhibited. At last, it was confirmed that cisatracurium could not alter the gene or protein expression level of Chrna1, but could block the ion channel. Overexpression of Chrna1 abolished the effect of cisatracurium on hyperhidrosis, while cisatracurium could not function more in siChrna1treated mice. Conclusion: Our results suggested that pretreatment of cisatracurium could alleviate hyperhidrosis in mice, probably through blocking the ion channel function of Chrna1.

show abstract

“…The piperazine group was next employed as a synthetic handle to further incorporate hydrogen bond acceptors. Examination of a variety of functional groups at the N-4 position identified amide, urea, and carbamate moieties provide inhibitors with good ALK2 activity (e.g., [8][9][10][11][12][13]. From this series of compounds, urea 11 (pSMAD1 IC 50 = 39 nM) and carbamate 12 (pSMAD1 IC 50 = 27 nM) displaying 10-fold improvement in cellular potency over 5 were selected for further characterization.…”

mentioning

confidence: 99%

“…Recent studies have identified that targeting BMP-SMAD signaling with ALK2/3 inhibitors could offer an effective therapeutic approach to improve the phenotype of iron-refractory iron-deficiency anemia . Additional disorders, such as diffuse idiopathic skeletal hyperostosis and primary focal hyperhidrosis have also been found to be associated with ALK2 overactivation. , Although several inhibitors of ALK2 have been reported as potential therapeutic agents, their development was hindered because of low selectivity against other ALK subtypes. − Herein, we report discovery of a novel pyrazolo[4,3- d ]pyrimidine series as potent, selective, and orally bioavailable inhibitors of ALK2 …”

mentioning

confidence: 99%

Discovery of Novel Pyrazolopyrimidines as Potent, Selective, and Orally Bioavailable Inhibitors of ALK2

Nguyen

Atasoylu

et al. 2022

ACS Med. Chem. Lett.

View full text Add to dashboard Cite

Activin receptor-like kinase 2 (ALK2) is a transmembrane kinase receptor that mediates the signaling of the members of the TGF-β superfamily. The aberrant activation of ALK2 has been linked to the rare genetic disorder fibrodysplasia ossificans progressiva (FOP) and diffuse intrinsic pontine glioma (DIPG) that are associated with severely reduced life expectancy in pediatric patients. ALK2 has also been shown to play an essential role in iron metabolism by regulating hepcidin levels and affecting anemia of chronic disease. Thus, selective inhibition of ALK2 has emerged as a promising strategy for the treatment of multiple disorders. Herein, we report the discovery of a novel pyrazolopyrimidines series as highly potent, selective, and orally bioavailable inhibitors of ALK2. Structure-based drug design and systematic structure−activity relationship studies were employed to identify potent inhibitors displaying high selectivity against other ALK subtypes with good pharmacokinetic profiles.

show abstract

Involvement of activin a receptor type 1 (ACVR1) in the pathogenesis of primary focal hyperhidrosis

Cited by 11 publications

References 29 publications

Efficacy and Safety of Radiofrequency Ablation Versus Video-assisted Thoracoscopic Sympathectomy in Palmar Hyperhidrosis: A Multicenter Cohort Study

Efficacy and Safety of Radiofrequency Ablation Versus Video-assisted Thoracoscopic Sympathectomy in Palmar Hyperhidrosis: A Multicenter Cohort Study

Antagonist of Chrna1 prevents the pathogenesis of primary focal hyperhidrosis

Discovery of Novel Pyrazolopyrimidines as Potent, Selective, and Orally Bioavailable Inhibitors of ALK2

Contact Info

Product

Resources

About