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Calcific aortic valve disease (CAVD) and coronary artery disease (CAD) are related cardiovascular diseases in which common mechanisms lead to tissue calcification. Oxidative stress plays a key role in these diseases and there is also evidence that the redox state of serum albumin exerts a significant influence on these conditions. To further explore this issue, we used multimarker scores (OxyScore and AntioxyScore) to assess the global oxidative status in patients with CAVD, with and without CAD, also evaluating their plasma thiol levels. In addition, valvular interstitial cells were treated with reduced, oxidized, and native albumin to study how this protein and its modifications affect cell calcification. The differences we found suggest that oxidative status is distinct in CAVD and CAD, with differences in redox markers and thiol levels. Importantly, the in vitro interstitial cell model revealed that modified albumin affects cell calcification, accelerating this process. Hence, we show here the importance of the redox system in the development of CAVD, emphasizing the relevance of multimarker scores, while also offering evidence of how the redox state of albumin influences vascular calcification. These data highlight the relevance of understanding the overall redox processes involved in these diseases, opening the door to new studies on antioxidants as potential therapies for these patients. [ABSTRACT FROM AUTHOR]

Encouraging recent data on the molecular pathways underlying aging have identified variants and expansions of genes associated with DNA replication and repair, telomere and stem cell maintenance, regulation of the redox microenvironment, and intercellular communication. In addition, cell rejuvenation requires silencing some transcription factors and the activation of pluripotency, indicating that hidden molecular networks must integrate and synchronize all these cellular mechanisms. Therefore, in addition to gene sequence expansions and variations associated with senescence, the optimization of transcriptional regulation and protein crosstalk is essential. The protein cysteinome is crucial in cellular regulation and plays unexpected roles in the aging of complex organisms, which show cumulative somatic mutations, telomere attrition, epigenetic modifications, and oxidative dysregulation, culminating in cellular senescence. The cysteine thiol groups are highly redox-active, allowing high functional versatility as structural disulfides, redox-active disulfides, active-site nucleophiles, proton donors, and metal ligands to participate in multiple regulatory sites in proteins. Also, antioxidant systems control diverse cellular functions, including the transcription machinery, which partially depends on the catalytically active cysteines that can reduce disulfide bonds in numerous target proteins, driving their biological integration. Since we have previously proposed a fundamental role of cysteine-mediated redox deregulation in neurodegeneration, we suggest that cellular rejuvenation of the cysteine redox proteome using GSH precursors, like N-acetyl-cysteine, is an underestimated multitarget therapeutic approach that would be particularly beneficial in Parkinson's disease. [ABSTRACT FROM AUTHOR]

In the last twenty years, significant progress in understanding the pathophysiology of age-associated neurodegenerative diseases has been made. However, the prevention and treatment of these diseases remain without clinically significant therapeutic advancement. While we still hope for some potential genetic therapeutic approaches, the current reality is far from substantial progress. With this state of the issue, emphasis should be placed on early diagnosis and prompt intervention in patients with increased risk of neurodegenerative diseases to slow down their progression, poor prognosis, and decreasing quality of life. Accordingly, it is urgent to implement interventions addressing the psychosocial and biochemical disturbances we know are central in managing the evolution of these disorders. Genomic and proteomic studies have shown the high molecular intricacy in neurodegenerative diseases, involving a broad spectrum of cellular pathways underlying disease progression. Recent investigations indicate that the dysregulation of the sensitive-cysteine proteome may be a concurrent pathogenic mechanism contributing to the pathophysiology of major neurodegenerative diseases, opening new therapeutic opportunities. Considering the incidence and prevalence of these disorders and their already significant burden in Western societies, they will become a real pandemic in the following decades. Therefore, we propose large-scale investigations, in selected groups of people over 40 years of age with decreased blood glutathione levels, comorbidities, and/or mild cognitive impairment, to evaluate supplementation of the diet with low doses of N-acetyl-cysteine, a promising and well-tolerated therapeutic agent suitable for long-term use. [ABSTRACT FROM AUTHOR]