Antiglycative Activity and RAGE Expression in Rett Syndrome

Cordone, Valeria; Pecorelli, Alessandra; Benedusi, Mascia; Santini, Silvano Junior; Falone, Stefano; Hayek, Joussef; Amicarelli, Fernanda; Valacchi, Giuseppe

doi:10.3390/cells8020161

Cited by 8 publications

(4 citation statements)

References 73 publications

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“…As previously reported [28], total RNA was extracted from fibroblasts by using Aurum Total RNA Mini Kit (cat.732–6820, Bio-Rad), removing genomic contamination by using DNase I, as recommended by the supplier. RNA (1 μg) was converted into complementary DNA by using iScript Reverse Transcription kit (cat.…”

Section: Methodsmentioning

confidence: 99%

Altered inflammasome machinery as a key player in the perpetuation of Rett syndrome oxinflammation

et al. 2020

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Rett syndrome (RTT) is a progressive neurodevelopmental disorder mainly caused by mutations in the X-linked MECP2 gene. RTT patients show multisystem disturbances associated with an oxinflammatory status. Inflammasomes are multi-protein complexes, responsible for host immune responses against pathogen infections and redox-related cellular stress. Assembly of NLRP3/ASC inflammasome triggers pro-caspase-1 activation, thus, resulting in IL-1β and IL-18 maturation. However, an aberrant activation of inflammasome system has been implicated in several human diseases. Our aim was to investigate the possible role of inflammasome in the chronic subclinical inflammatory condition typical of RTT, by analyzing this complex in basal and lipopolysaccharide (LPS)+ATP-stimulated primary fibroblasts, as well as in serum from RTT patients and healthy volunteers. RTT cells showed increased levels of nuclear p65 and ASC proteins, pro-IL-1β mRNA, and NLRP3/ASC interaction in basal condition, without any further response upon the LPS + ATP stimuli. Moreover, augmented levels of circulating ASC and IL-18 proteins were found in serum of RTT patients, which are likely able to amplify the inflammatory response. Taken together, our findings suggest that RTT patients exhibited a challenged inflammasome machinery at cellular and systemic level, which may contribute to the subclinical inflammatory state feedback observed in this pathology.

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Section: Methodsmentioning

confidence: 99%

Altered inflammasome machinery as a key player in the perpetuation of Rett syndrome oxinflammation

et al. 2020

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“…Of importance, albeit the neurodegenerative diseases have not been covered at the present work, evidences suggest that propolis components (i.e., pinocembrin) may also provide neuroprotection against neurotoxicity mechanisms related to advanced glycation end products (AGEs) and consequent mitochondrial dysfunction 32,80‐82 . Such interesting findings deserve further investigation in future studies.…”

Section: Neuropharmacological Effectsmentioning

confidence: 81%

Propolis: A useful agent on psychiatric and neurological disorders? A focus on CAPE and pinocembrin components

Silveira

Luz

Silva

et al. 2020

Medicinal Research Reviews

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Propolis consists of a honeybee product, with a complex mix of substances that have been widely used in traditional medicine. Among several compounds present in propolis, caffeic acid phenethyl ester (CAPE), and pinocembrin emerge as two principal bioactive compounds, with benefits in a variety of body systems. In addition to its well‐explored pharmacological properties, neuropharmacological activities have been poorly discussed. In an unprecedented way, the present review addresses the current finding on the promising therapeutic purposes of propolis, focusing on CAPE and pinocembrin, highlighting its use on neurological disturbance, as cerebral ischemia, neuroinflammation, convulsion, and cognitive impairment, as well as psychiatric disorders, such as anxiety and depression. In addition, we provide a critical analysis, discussion, and systematization of the molecular mechanisms which underlie these central nervous system effects. We hypothesize that the pleiotropic action of CAPE and pinocembrin, per se or associated with other substances present in propolis may result in the therapeutic activities reported. Inhibition of the pro‐inflammatory cascade, antioxidant activity, and positive neurotrophic modulatory effects consist of the main molecular targets attributed to CAPE and pinocembrin in health benefits.

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“…These ROS spectacularly inhibit GLO I, ushering in the intracellular buildup of pro-apoptotic AGEs, such as argpyrimidine, and kickstarting a mitochondrialdependent apoptotic pathway [21][22][23][24]. One important component of a process that produces particular MG-derived AGEs is phosphorylated GLO I [25]. Adding another layer to this genetic symphony, GLO I expression encounters modulation through the RAGE receptor being activated, though the specifics of this maneuver remain veiled [13,16].…”

Section: Glyoxalase Imentioning

confidence: 99%

Molecular Assessment of Methylglyoxal-Induced Toxicity and Therapeutic Approaches in Various Diseases: Exploring the Interplay with the Glyoxalase System

Alhujaily

2024

Life

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This comprehensive exploration delves into the intricate interplay of methylglyoxal (MG) and glyoxalase 1 (GLO I) in various physiological and pathological contexts. The linchpin of the narrative revolves around the role of these small molecules in age-related issues, diabetes, obesity, cardiovascular diseases, and neurodegenerative disorders. Methylglyoxal, a reactive dicarbonyl metabolite, takes center stage, becoming a principal player in the development of AGEs and contributing to cell and tissue dysfunction. The dual facets of GLO I—activation and inhibition—unfold as potential therapeutic avenues. Activators, spanning synthetic drugs like candesartan to natural compounds like polyphenols and isothiocyanates, aim to restore GLO I function. These molecular enhancers showcase promising outcomes in conditions such as diabetic retinopathy, kidney disease, and beyond. On the contrary, GLO I inhibitors emerge as crucial players in cancer treatment, offering new possibilities in diseases associated with inflammation and multidrug resistance. The symphony of small molecules, from GLO I activators to inhibitors, presents a nuanced understanding of MG regulation. From natural compounds to synthetic drugs, each element contributes to a molecular orchestra, promising novel interventions and personalized approaches in the pursuit of health and wellbeing. The abstract concludes with an emphasis on the necessity of rigorous clinical trials to validate these findings and acknowledges the importance of individual variability in the complex landscape of health.

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Antiglycative Activity and RAGE Expression in Rett Syndrome

Cited by 8 publications

References 73 publications

Altered inflammasome machinery as a key player in the perpetuation of Rett syndrome oxinflammation

Altered inflammasome machinery as a key player in the perpetuation of Rett syndrome oxinflammation

Propolis: A useful agent on psychiatric and neurological disorders? A focus on CAPE and pinocembrin components

Molecular Assessment of Methylglyoxal-Induced Toxicity and Therapeutic Approaches in Various Diseases: Exploring the Interplay with the Glyoxalase System

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