Unraveling the Role of Receptor for Advanced Glycation End Products (RAGE) and Its Ligands in Myasthenia Gravis

Angelopoulou, Efthalia; Paudel, Yam Nath; Piperi, Christina

doi:10.1021/acschemneuro.9b00678

Cited by 10 publications

(9 citation statements)

References 71 publications

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“…Our present study demonstrated AIH patients exhibited elevated EN-RAGE and reduced sRAGE levels along with increased RAGE/sRAGE value in a well-defined cohort, indicating that EN-RAGE and sRAGE may exert opposite functions on regulating the AIH pathogenesis. This finding supports previous studies showing high EN-RAGE or low sRAGE levels in other inflammatory-immune disorders [23][24][25]. Based on data from assessment of differentiating power of EN-RAGE, sRAGE and EN-RAGE/ sRAGE for AIH by ROC analysis, we identified EN-RAGE/sRAGE had the highest diagnostic efficacy.…”

Section: Discussionsupporting

confidence: 90%

Assessment of EN-RAGE, sRAGE and EN-RAGE/sRAGE as potential biomarkers in patients with autoimmune hepatitis

Liu

Yan

et al. 2020

J Transl Med

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Background Autoimmune hepatitis (AIH) is a liver disease characterized by the autoimmune-induced injury of hepatocytes which can lead to cirrhosis and hepatic failure. The diagnosis and disease management of AIH patients remain challenging due to the diversity of clinical phenotypes and the presence of confounders such as alcohol and viruses. Recently, EN-RAGE and sRAGEs have been implicated in inflammatory-immune response. Nonetheless, their natural behaviour and relationship to disease activity as well as clinical predictive values in AIH development or therapy-induced remission have not been reported. Methods Sixty-seven AIH patients and thirty gender- and age-matched healthy controls (HC) were enrolled. The serum concentrations of EN-RAGE, sRAGE and their ratio (EN-RAGE/sRAGE) in these subjects were measured by ELISA. Besides, the correlations of three parameters with clinical features and therapeutic response were analyzed, respectively. Furthermore, their potential predictive values for monitoring the AIH progression and therapeutic response were also evaluated. Results Higher serum EN-RAGE, lower sRAGE and higher EN-RAGE/sRAGE value were observed in AIH patients. EN-RAGE and sRAGE as well as EN-RAGE/sRAGE were correlated with liver necroinflammation parameters, cirrhosis occurrence and therapeutic response. In addition, we identified that EN-RAGE/sRAGE, EN-RAGE and sRAGE had valuable predicting power for AIH patients, AIH patients with normal ALT and cirrhosis incidence, respectively. More importantly, EN-RAGE/sRAGE also exerted predicting power for the remission in AIH patients. Conclusions AIH patients rendered distinct patterns of serum EN-RAGE, sRAGE or EN-RAGE/sRAGE compared to healthy controls. Moreover, these three parameters exhibited potentials as novel biomarkers for AIH diagnosis and prognosis evaluation.

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Section: Discussionsupporting

confidence: 90%

Assessment of EN-RAGE, sRAGE and EN-RAGE/sRAGE as potential biomarkers in patients with autoimmune hepatitis

Liu

Yan

et al. 2020

J Transl Med

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“…Our results are in line with a previous study in myasthenia gravis where S100B-mediated RAGE activation exacerbated the disease by enhancing T cell pro-inflammatory responses and aggravating T helper subset imbalance. 51 Therefore, modulation of S100B expression at both the CNS and peripheral level may be a beneficial therapeutic strategy to reduce multiple sclerosis-associated pathology.…”

Section: Discussionmentioning

confidence: 99%

S100B inhibition protects from chronic experimental autoimmune encephalomyelitis

Barros

Barateiro

Trofino

et al. 2022

Brain Communications

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Studies have correlated excessive S100B, a small inflammatory molecule, with demyelination and associated inflammatory processes occurring in multiple sclerosis. The relevance of S100B in multiple sclerosis pathology brought an emerging curiosity highlighting its use as a potential therapeutic target to reduce damage during the multiple sclerosis course, namely during inflammatory relapses. We examined the relevance of S100B and further investigated the potential of S100B-neutralizing small molecule pentamidine in chronic experimental autoimmune encephalomyelitis. S100B depletion had beneficial pathological outcomes and, based on promising results of a variety of S100B-blockade strategies in an ex vivo demyelinating model we choose pentamidine to assay its role in the in vivo experimental autoimmune encephalomyelitis. We report that pentamidine prevents more aggressive clinical symptoms and improves recovery of chronic experimental autoimmune encephalomyelitis. Blockade of S100B by pentamidine protects against oligodendrogenesis impairment and neuroinflammation by reducing astrocyte reactivity and microglia pro-inflammatory phenotype. Pentamidine also increased regulatory T cell density in the spinal cord suggesting an additional immunomodulatory action. These results showed the relevance of S100B as a main driver of neuroinflammation in experimental autoimmune encephalomyelitis and identified an uncharacterized mode of action of pentamidine, strengthening the possibility to use this drug as an anti-inflammatory and remyelinating therapy for progressive multiple sclerosis.

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“…Aberrant overexpression of RAGE stimulated by several ligands triggers inflammation and oxidative stress, resulting to pathological conditions in muscle. For instance, increased levels of S-100B (one RAGE ligand) and RAGE are observed in experimental animal models of myasthenia gravis [ 26 , 27 ]; and overexpression of HMGB1, CML(both RAGE ligands), and RAGE was found in the muscle fibers of polymyositis and dermatomyositis patients [ 28 , 29 ]. As for sRAGE, a Korean study revealed the association between low levels of sRAGE and low muscle mass, suggesting a protective role of sRAGE against sarcopenia [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

Elevated level of the soluble receptor for advanced glycation end-products involved in sarcopenia: an observational study

Chiu

Kao

et al. 2021

BMC Geriatr

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Background The soluble receptor for advanced glycation end products (sRAGE) has been proposed to serve as a marker for disease severity, but its role in sarcopenia, an age-related progressive loss of muscle mass and function, remains elusive. This study examines the association between sRAGE and sarcopenia. Methods A total of 314 community-dwelling elderly adults who had their health examination at Tri-Service General Hospital from 2017 to 2019 underwent protein analysis with enzyme-linked immunosorbent assay. The relationship with sarcopenia and its detailed information, including components and diagnosis status, were examined using linear and logistic regressions. Results As for sarcopenia components, low muscle mass (β = 162.8, p = 0.012) and strength (β = 181.31, p = 0.011) were significantly correlated with sRAGE, but not low gait speed (p = 0.066). With regard to disease status, confirmed sarcopenia (β = 436.93, p < 0.001), but not probable (p = 0.448) or severe sarcopenia (p = 0.488), was significantly correlated with sRAGE. In addition, females revealed a stronger association with sRAGE level by showing significant correlations with low muscle mass (β = 221.72, p = 0.014) and low muscle strength (β = 208.68, p = 0.043). Conclusions sRAGE level showed a positive association with sarcopenia, illustrating its involvement in the evolution of sarcopenia. This association is more evident in female groups, which may be attributed to the loss of protection from estrogen in postmenopausal women. Utilizing sRAGE level as a prospective marker for sarcopenia deserves further investigation in future studies.

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Unraveling the Role of Receptor for Advanced Glycation End Products (RAGE) and Its Ligands in Myasthenia Gravis

Cited by 10 publications

References 71 publications

Assessment of EN-RAGE, sRAGE and EN-RAGE/sRAGE as potential biomarkers in patients with autoimmune hepatitis

Assessment of EN-RAGE, sRAGE and EN-RAGE/sRAGE as potential biomarkers in patients with autoimmune hepatitis

S100B inhibition protects from chronic experimental autoimmune encephalomyelitis

Elevated level of the soluble receptor for advanced glycation end-products involved in sarcopenia: an observational study

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