The importance of Saccharomyces cerevisiae yeast cells is known worldwide, as they are the most used microorganisms in biotechnology for bioethanol and biofuel production. Also, they are analyzed and studied for their similar internal biochemical processes to human cells, for a better understanding of cell aging and response to cell stressors. The special ability of S. cerevisiae cells to develop in both aerobic and anaerobic conditions makes this microorganism a viable model to study the transformations and the way in which cellular metabolism is directed to face the stress conditions due to environmental changes. Thus, this review will emphasize the effects of oxidative, ethanol, and osmotic stress and also the physiological and genetic response of stress mitigation in yeast cells.

Microbiota-derived hydrogen sulfide (H₂S) plays a crucial role in modulating the gut–brain axis, with significant implications for neurodegenerative diseases such as Alzheimer’s and Parkinson’s. H₂S is produced by sulfate-reducing bacteria in the gut and acts as a critical signaling molecule influencing brain health via various pathways, including regulating inflammation, oxidative stress, and immune responses. H₂S maintains gut barrier integrity at physiological levels and prevents systemic inflammation, which could impact neuroinflammation. However, as H₂S has a dual role or a Janus face, excessive H₂S production, often resulting from gut dysbiosis, can compromise the intestinal barrier and exacerbate neurodegenerative processes by promoting neuroinflammation and glial cell dysfunction. This imbalance is linked to the early pathogenesis of Alzheimer’s and Parkinson’s diseases, where the overproduction of H₂S exacerbates beta-amyloid deposition, tau hyperphosphorylation, and alpha-synuclein aggregation, driving neuroinflammatory responses and neuronal damage. Targeting gut microbiota to restore H₂S homeostasis through dietary interventions, probiotics, prebiotics, and fecal microbiota transplantation presents a promising therapeutic approach. By rebalancing the microbiota-derived H₂S, these strategies may mitigate neurodegeneration and offer novel treatments for Alzheimer’s and Parkinson’s diseases, underscoring the critical role of the gut–brain axis in maintaining central nervous system health.

Neurodegenerative diseases encompass a spectrum of disorders marked by the progressive degeneration of the structure and function of the nervous system. These conditions, including Parkinson’s disease (PD), Alzheimer’s disease (AD), Huntington’s disease (HD), Amyotrophic lateral sclerosis (ALS), and Multiple sclerosis (MS), often lead to severe cognitive and motor deficits. A critical component of neurodegenerative disease pathologies is the imbalance between pro-oxidant and antioxidant mechanisms, culminating in oxidative stress. The brain’s high oxygen consumption and lipid-rich environment make it particularly vulnerable to oxidative damage. Pro-oxidants such as reactive nitrogen species (RNS) and reactive oxygen species (ROS) are continuously generated during normal metabolism, counteracted by enzymatic and non-enzymatic antioxidant defenses. In neurodegenerative diseases, this balance is disrupted, leading to neuronal damage. This systematic review explores the roles of oxidative stress, gut microbiota, and epigenetic modifications in neurodegenerative diseases, aiming to elucidate the interplay between these factors and identify potential therapeutic strategies. We conducted a comprehensive search of articles published in 2024 across major databases, focusing on studies examining the relationships between redox homeostasis, gut microbiota, and epigenetic changes in neurodegeneration. A total of 161 studies were included, comprising clinical trials, observational studies, and experimental research. Our findings reveal that oxidative stress plays a central role in the pathogenesis of neurodegenerative diseases, with gut microbiota composition and epigenetic modifications significantly influencing redox balance. Specific bacterial taxa and epigenetic markers were identified as potential modulators of oxidative stress, suggesting novel avenues for therapeutic intervention. Moreover, recent evidence from human and animal studies supports the emerging concept of targeting redox homeostasis through microbiota and epigenetic therapies. Future research should focus on validating these targets in clinical settings and exploring the potential for personalized medicine strategies based on individual microbiota and epigenetic profiles.

The intricate relationship between hydrogen sulfide (H2S), gut microbiota, and sirtuins (SIRTs) can be seen as a paradigm axis in maintaining cellular homeostasis, modulating oxidative stress, and promoting mitochondrial health, which together play a pivotal role in aging and neurodegenerative diseases. H2S, a gasotransmitter synthesized endogenously and by specific gut microbiota, acts as a potent modulator of mitochondrial function and oxidative stress, protecting against cellular damage. Through sulfate-reducing bacteria, gut microbiota influences systemic H2S levels, creating a link between gut health and metabolic processes. Dysbiosis, or an imbalance in microbial populations, can alter H2S production, impair mitochondrial function, increase oxidative stress, and heighten inflammation, all contributing factors in neurodegenerative diseases such as Alzheimer’s and Parkinson’s. Sirtuins, particularly SIRT1 and SIRT3, are NAD+-dependent deacetylases that regulate mitochondrial biogenesis, antioxidant defense, and inflammation. H2S enhances sirtuin activity through post-translational modifications, such as sulfhydration, which activate sirtuin pathways essential for mitigating oxidative damage, reducing inflammation, and promoting cellular longevity. SIRT1, for example, deacetylates NF-κB, reducing pro-inflammatory cytokine expression, while SIRT3 modulates key mitochondrial enzymes to improve energy metabolism and detoxify reactive oxygen species (ROS). This synergy between H2S and sirtuins is profoundly influenced by the gut microbiota, which modulates systemic H2S levels and, in turn, impacts sirtuin activation. The gut microbiota–H2S–sirtuin axis is also essential in regulating neuroinflammation, which plays a central role in the pathogenesis of neurodegenerative diseases. Pharmacological interventions, including H2S donors and sirtuin-activating compounds (STACs), promise to improve these pathways synergistically, providing a novel therapeutic approach for neurodegenerative conditions. This suggests that maintaining gut microbiota diversity and promoting optimal H2S levels can have far-reaching effects on brain health.

Atherosclerosis is a chronic inflammatory condition marked by endothelial dysfunction, lipid accumulation, inflammatory cell infiltration, and extracellular matrix (ECM) remodeling within arterial walls, leading to plaque formation and potential cardiovascular events. Key players in ECM remodeling and inflammation are matrix metalloproteinases (MMPs) and CD147/EMMPRIN, a cell surface glycoprotein expressed on endothelial cells, vascular smooth muscle cells (VSMCs), and immune cells, that regulates MMP activity. Hydrogen sulfide (H₂S), a gaseous signaling molecule, has emerged as a significant modulator of these processes including oxidative stress mitigation, inflammation reduction, and vascular remodeling. This systematic review investigates the mechanistic pathways through which H₂S influences MMPs and CD147/EMMPRIN and assesses its impact on atherosclerosis progression. A comprehensive literature search was conducted across PubMed, Scopus, and Web of Science databases, focusing on studies examining H₂S modulation of MMPs and CD147/EMMPRIN in atherosclerosis contexts. Findings indicate that H₂S modulates MMP expression and activity through transcriptional regulation and post-translational modifications, including S-sulfhydration. By mitigating oxidative stress, H₂S reduces MMP activation, contributing to plaque stability and vascular remodeling. H₂S also downregulates CD147/EMMPRIN expression via transcriptional pathways, diminishing inflammatory responses and vascular cellular proliferation within plaques. The dual regulatory role of H₂S in inhibiting MMP activity and downregulating CD147 suggests its potential as a therapeutic agent in stabilizing atherosclerotic plaques and mitigating inflammation. Further research is warranted to elucidate the precise molecular mechanisms and to explore H₂S-based therapies for clinical application in atherosclerosis.

Oxidative stress, a state resulting from an imbalance between the generation of reactive oxygen species (ROS) and the body’s antioxidant capacity, is a significant contributor to the development of various human pathologies, including malignancies, cardiovascular conditions, neurodegenerative disorders, and the aging process. Antioxidants, both enzymatic and non-enzymatic, are vital in neutralizing free radicals and protecting against cellular damage. Given the limitations of synthetic antioxidants, such as potential toxicity and variable effectiveness, there has been a growing focus on biotechnological methods for producing these essential compounds. This review, titled “Engineering Antioxidants with Pharmacological Applications: Biotechnological Perspectives”, explores the latest developments in this field by examining how biological systems are being utilized to create a wide range of antioxidants. We discuss key production strategies, including the use of microbial cell factories, enzyme-driven synthesis, plant cell cultures, and metabolic engineering. The review provides specific examples of biotechnologically derived antioxidants, such as enzymatic defenses like superoxide dismutase, catalase, and glutathione peroxidase, as well as non-enzymatic molecules like carotenoids, polyphenols, and vitamins. We also evaluate the therapeutic potential of these bio-engineered antioxidants, analyzing preclinical and clinical data on their effectiveness in disease prevention and treatment. The mechanisms by which these compounds combat oxidative stress are also discussed. Finally, we address the current hurdles in scaling up production and managing costs while also outlining future research avenues, such as the creation of new production systems, advanced delivery technologies, and the discovery of novel antioxidant compounds through bioprospecting and synthetic biology. This comprehensive review highlights the potential of biotechnology to offer sustainable and impactful solutions for managing oxidative stress and enhancing overall health.