The Redox Medicine Society is pleased to announce an important international collaboration between leading research institutions: the University of Groningen Medical Center (UMCG), the National Institute on Aging in Baltimore, USA; the University of Copenhagen, Denmark; and the ISTCT, CNRS, Université de Caen Normandie, France. This study, led by Prof. Amalia Dolga’s lab at UMCG, explores the therapeutic potential of Nicotinamide Riboside (NR), a precursor of nicotinamide adenine dinucleotide (NAD+), in preventing neuronal ferroptosis and modulating crucial biochemical pathways in the brain.

The research revealed that NR effectively prevents neuronal ferroptosis, a form of cell death linked to neurodegenerative diseases. Additionally, NR modulates the bioenergetic status and reactive species interactome (RSI) within the brain, influencing critical aspects of cellular metabolism and stress response. The study also found that NR treatment leads to significant, region-specific changes in the brain’s proteomic landscape, particularly within the cortex and hippocampus, regions most affected by AD.

Moreover, the research established a correlation between protein co-expression modules altered by NR treatment and ATP production, along with various reactive species. These findings contribute to a deeper understanding of how NR influences the metabolome and proteome in Alzheimer’s Disease, potentially offering new avenues for disease modification and therapy.

Commenting on the study, Dr. Laurent Chatre, co-author and active member of the RMS Scientific Board, commented: “This paper opens up new perspectives on Alzheimer’s Disease, well beyond the traditional beta-amyloid-centered view, which has ultimately not led to therapeutic breakthroughs. The RSI and mitochondria are key players in this disease, presenting new opportunities for biomarkers, therapeutic targets, and personalized medicine”.

Read the full paper: https://doi.org/10.1016/j.nbd.2024.106645.

Photo credits: Dr. Laurent Chatre.

Tomin et al. (Vienna University of Technology) have conducted a groundbreaking study using mass spectrometry to analyze the redox state and protein profiles of failing human hearts. Oxidative stress, a key factor in heart failure, damages the myocardium, impairs antioxidant defenses, disrupts redox signaling, and harms proteins.

The study involved comprehensive analyses of left-ventricular tissue from both healthy and failing human hearts. The findings revealed that failing hearts have lower ratios of glutathione to glutathione disulfide and increased oxidation of various proteins, including those involved in contraction and glycolysis. Additionally, quantitative proteomics showed an increased presence of proteins linked to extracellular matrix remodeling and a decrease in several ion transporters, aligning with observed contractile impairment.

These effects were also replicated in an in vitro cell culture model under controlled oxygen conditions. This study is the most extensive to date, integrating analyses of protein abundance, redox state, and global proteome profiles in end-stage failing human hearts and cultured human cardiomyocytes.

Article DOI.

Scientists have used a huge database to find links between existing drugs and human lifespan. Only 14 of more than 400 showed a positive correlation [1].

Reinventing the wheel?

One of the subfields in geroscience was born from the idea that some drugs currently in use for various indications might slow aging. In recent years, we have seen such successes with existing drugs in animal models. For instance, rapamycin, which is mostly used as an immunosuppressant, is one of the strongest pro-longevity interventions in mice.

What about people? Unfortunately, there hasn’t been a single lifespan clinical study in humans. Designing such a trial is difficult due to our species’ remarkable longevity. Hence, our only current option is populational studies of people who take medicines.

One such study had caused a lot of fuss around the anti-diabetes drug metformin, as it showed that diabetes patients who received the drug lived longer than healthy people who did not [2]. Since then, another study has cast those results into doubt [3]. Metformin also failed to increase lifespan in mice in a rigorous trial that was conducted as part of the Interventions Testing Program (ITP).

The fabulous 14

Finally, a large-scale populational study of associations between various drugs and human lifespan is out as a pre-print (that is, it has not been peer-reviewed yet). The authors, which include the renowned geroscientist Alejandro Ocampo, used data from UK Biobank, a huge repository of health data on half a million of British citizens.

UK Biobank contains drug prescriptions for more than 200,000 participants (56 million prescriptions in total). This allowed the researchers to analyze the effects of 406 drugs prescribed to at least 500 patients each. 169 of the drugs had an effect on lifespan. Most were, predictably, associated with shorter lifespan. This is a known phenomenon caused, probably, by the diseases that drugs are prescribed for and by the drugs’ side effects.

However, 14 drugs appeared to positively influence lifespan compared to health-matched controls. The researchers controlled for major factors known to influence lifespan: current smoking status, cancer diagnosis, diabetes, gender, and age at recruitment.

One of the drugs was atorvastatin. This is one of the statins, a class of drugs used to decrease the levels of cholesterol in the blood. Statins have a good safety profile and are generally considered one of modern medicine’s biggest successes. Use of atorvastatin was associated with 9% less mortality risk (hazard ratio of 0.91).

Another winner was naproxen, a non-steroidal anti-inflammatory drug (NSAID) used to ease symptoms of arthritis. It was associated with a 10% decrease in mortality risk. Chronic inflammation is one of the hallmarks of aging and a driver of multiple aging processes. However, we cannot be sure this is the reason for naproxen making the cut. Another anti-inflammatory drug on the list was Otomize, a spray used to treat ear infections with three active ingredients, including steroids.

Something for both sexes

Another well-known drug to be found associated with longer lifespan was sildenafil, also known as Viagra, with a 15% less mortality risk. Again, we do not know the reason. It could be Viagra’s vessel-diluting activity or a case of reverse causation, in which healthier people are more interested in having sex.

Sildenafil, of course, is only prescribed to the male population, but women had their winners too. Those were estrogen-related drugs: Estraderm, Vagifem, estriol, and estradiol. They seemed to have a profound effect, decreasing mortality risk by 33%, 27%, 26%, and 25% respectively. Recent research has shown that menopause and dwindling levels of estrogen associated with it are linked to poorer health, which is improved by hormone replacement therapy (HRT). Interestingly, 17-alpha-estradiol, a “non-feminizing estrogen”, has produced notable life extension in male but not female mice [4].

The three last drugs linked to less mortality risk were the contraceptive Marvelon and two vaccines, Avaxim and Revaxis. The authors specifically note that metformin did not have any effect on lifespan. The study does not mention rapamycin, probably because it is rarely prescribed.

The researchers also looked at classes of drugs. Statins as a class were negatively associated with mortality risk, and even more so were SGLT2 inhibitors, a class of anti-diabetes drugs (36% risk reduction, but in a smaller sample than metformin). The most popular commercial SGLT2 inhibitor is Jardiance (empagliflozin). Another drug of this family, canagliflozin, led to life extension in mice in ITP trials [5].

Populational studies like this one are notoriously hard to interpret and can show correlation but not causation. The researchers controlled for just a handful of confounding variables, and many more factors were probably unaccounted for. However, as the data gets bigger and better, we should see more studies that point to existing drugs as possible geroprotectors.

Literature

[1] Morin, J., Rolland, Y., Bischoff-Ferrari, H. A., Ocampo, A., & Perez, K. (2024). Association between prescription drugs and all-cause mortality risk in the UK population. medRxiv, 2024-03. 

[2] Bannister, C. A., Holden, S. E., Jenkins‐Jones, S., Morgan, C. L., Halcox, J. P., Schernthaner, G., … & Currie, C. J. (2014). Can people with type 2 diabetes live longer than those without? A comparison of mortality in people initiated with metformin or sulphonylurea monotherapy and matched, non‐diabetic controls. Diabetes, Obesity and Metabolism, 16(11), 1165-1173.

[3] Stevenson-Hoare, J., Leonenko, G., & Escott-Price, V. (2023). Comparison of long-term effects of metformin on longevity between people with type 2 diabetes and matched non-diabetic controls. BMC Public Health, 23(1), 804.

[4] Harrison, D. E., Strong, R., Reifsnyder, P., Kumar, N., Fernandez, E., Flurkey, K., … & Miller, R. A. (2021). 17‐a‐estradiol late in life extends lifespan in aging UM‐HET3 male mice; nicotinamide riboside and three other drugs do not affect lifespan in either sex. Aging Cell, 20(5), e13328.

[5] Miller, R. A., Harrison, D. E., Allison, D. B., Bogue, M., Debarba, L., Diaz, V., … & Strong, R. (2020). Canagliflozin extends life span in genetically heterogeneous male but not female mice. JCI insight, 5(21).

Source.

In a recent paper, Mugesh et al. have made significant strides in the realm of nanozymes, nanomaterials exhibiting enzyme-like functions. Nanozymes have garnered considerable attention due to their potential to replace natural enzymes across a spectrum of biomedical applications, including biosensing, therapeutics, drug delivery, and bioimaging.

Of particular interest are nanozymes capable of modulating cellular redox status by emulating antioxidant enzymes in mammalian cells. This capability holds promise for addressing oxidative-stress-related disorders. Distinguishing between physiological oxidative stress (oxidative eustress) and pathological oxidative stress (oxidative distress) poses a notable challenge. Designing nanozymes capable of discerning and reacting appropriately to these varying cellular conditions in cells, tissues, and organs is crucial.

In their review, Mugesh et al. outlined advancements in the development of redox-active nanozymes and their biomedical applications. They underscored the therapeutic significance of both antioxidant and prooxidant nanozymes in various disease models, including cancer, neurodegeneration, and cardiovascular diseases.

Looking ahead, they discussed future prospects in this burgeoning field and outline the challenges associated with the biomedical applications of nanozymes. Their work sheds light on the potential of nanozymes to revolutionize therapeutic interventions in oxidative-stress-mediated disorders, offering hope for improved treatment modalities in the future.

Photo Description:

This Review offers an overview of the recent development of redox-active nanozymes, primarily highlighting antioxidant and prooxidant nanozymes and their therapeutic significance in oxidative-stress-mediated disorders with an outlook on the current challenges and future trends. The insight provided should aid the development of next-generation therapeutic nanozymes for translation into clinical settings.

Photo Credits: Graphical Abstract N. Singh, G. R. Sherin, G. Mugesh, Angew. Chem. Int. Ed. 2023

Article DOI.

A new systematic review by Cristina Estornut and colleagues, published in the Journal of Molecular Medicine in February 2024, focuses on the role of oxidative stress in recurrent aphthous stomatitis (RAS), a chronic and recurrent inflammatory condition of the mouth characterized by painful ulcers on the oral mucosa. Oxidative stress, resulting from an imbalance between free radicals and the antioxidant defense system, is implicated in the pathogenesis of RAS, alongside genetic predisposition, environmental factors, and immune system alterations. Various risk factors, including smoking, iron and vitamin deficiencies, and anxiety, may contribute to the disease's development.

Explanatory diagram of the process of appearance of oral cell damage through inflammatory induction and ROS production. Created with Biorender. Credits: Cristina Estornut et al., 2024.

To understand the systemic and local effects of oxidative stress on RAS, the researchers conducted a comprehensive literature search across PubMed, Scopus, and Web of Science, spanning from 2000 to 2023. They selected studies that analyzed oxidant and antioxidant levels in both blood and saliva samples of RAS patients compared to healthy controls. Out of 170 potentially relevant articles, 24 met the inclusion criteria, encompassing studies on blood (11 studies), saliva (6 studies), and both (7 studies).

The findings revealed statistically significant differences between RAS patients and healthy controls in multiple oxidative and antioxidant markers in both saliva and blood samples. Notably, there was an increased oxidative DNA damage in RAS patients, indicating elevated levels of oxidative stress compared to healthy individuals. These results suggest a significant increase in oxidative markers and a decrease in antioxidant defenses in individuals with RAS.

The study underscores the importance of understanding oxidative stress's role in RAS to develop prevention and treatment strategies. By highlighting the imbalance between oxidative and antioxidant markers in RAS patients, it points towards potential therapeutic interventions focusing on antioxidant supplementation or lifestyle modifications aimed at reducing oxidative stress, thus mitigating the disease's impact.

Redox Medicine 2024 will cover all strategies to control oxidative stress, as well as the role of antioxidants. Join the conference in June and submit a related abstract. 

Article DOI.

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Researchers led by Northwestern University and the University of Wisconsin-Madison have introduced a pioneering approach aimed at combating neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and Amyotrophic lateral sclerosis (ALS).

In a new study, researchers discovered a new way to enhance the body's antioxidant response, which is crucial for cellular protection against the oxidative stress implicated in many neurodegenerative diseases.

The study published today (February 16) in the journal Advanced Materials.

Nathan Gianneschi, the Jacob & Rosaline Cohn Professor of Chemistry at Northwestern's Weinberg College of Arts and Sciences and member of the International Institute for Nanotechnology, led the work with Jeffrey A. Johnson and Delinda A. Johnson of the University of Wisconsin-Madison School of Pharmacy.

Proteins are nature's polymers, governing biological processes at every level. A new study presents artificial proteins made using modern, precision polymers to intervene and alter natural processes towards a new way of developing therapeutics. Credit: Northwestern University/University of Wisconsin

Targeting neurodegenerative diseases

Alzheimer's disease, characterized by the accumulation of beta-amyloid plaques and tau protein tangles; Parkinson's disease, known for its loss of dopaminergic neurons and presence of Lewy bodies; and ALS, involving the degeneration of motor neurons, all share a common thread of oxidative stress contributing to disease pathology.

The study focuses on disrupting the Keap1/Nrf2 protein-protein interaction (PPI), which plays a role in the body's antioxidant response. By preventing the degradation of Nrf2 through selective inhibition of its interaction with Keap1, the research holds promise for mitigating the cellular damage that underlies these debilitating conditions.

"We established Nrf2 as a principal target for the treatment of neurodegenerative diseases over the past two decades, but this novel approach for activating the pathway holds great promise to develop disease-modifying therapies," Jeffrey Johnson said.

Limitations of current therapeutics

The research team embarked on addressing one of the most challenging aspects of neurodegenerative disease treatment: the precise targeting of PPIs within the cell. Traditional methods, including small molecule inhibitors and peptide-based therapies, have fallen short due to lack of specificity, stability and cellular uptake.

The study introduces an innovative solution: protein-like polymers, or PLPs, are high-density brush macromolecular architectures synthesized via the ring-opening metathesis polymerization (ROMP) of norbornenyl-peptide-based monomers. These globular, proteomimetic structures display bioactive peptide side chains that can penetrate cell membranes, exhibit remarkable stability and resist proteolysis.

This targeted approach to inhibit the Keap1/Nrf2 PPI represents a significant leap forward. By preventing Keap1 from marking Nrf2 for degradation, Nrf2 accumulates in the nucleus, activating the Antioxidant Response Element (ARE) and driving the expression of detoxifying and antioxidant genes. This mechanism effectively enhances the cellular antioxidant response, providing a potent therapeutic strategy against the oxidative stress implicated in many neurodegenerative diseases.

The innovation behind protein-like polymers

PLPs, developed by Gianneschi's team, could represent a significant breakthrough in halting or reversing damage offering hope for improved treatments and outcomes.

Focusing on the challenge of activating processes crucial for the body's antioxidant response, the team's research offers a novel solution. The team provides a robust, selective method enabling enhanced cellular protection and offering a promising therapeutic strategy for a range of diseases including neurodegenerative conditions.

"Through modern polymer chemistry, we can begin to think about mimicking complex proteins," Gianneschi said. "The promise lies in the development of a new modality for the design of therapeutics. This could be a way to address diseases like Alzheimer's and Parkinson's among others where traditional approaches have struggled."

This approach not only represents a significant advance in targeting transcription factors and disordered proteins, but also showcases the PLP technology's versatility and potential to revolutionize the development of therapeutics. The technology's modularity and efficacy in inhibiting the Keap1/Nrf2 interaction underscore its potential for impact as a therapeutic, but also as a tool for studying the biochemistry of these processes.

A collaboration of minds

Highlighting the study's collaborative nature, Gianneschi's team worked closely with experts across disciplines, illustrating the rich potential of combining materials science with cellular biology to tackle complex medical challenges.

"We were contacted by Professor Gianneschi and colleagues proposing to use this novel PLP technology in neurodegenerative diseases due to our previous work on Nrf2 in models of Alzheimer's disease, Parkinson's disease, ALS and Huntington's disease," Jeffrey Johnson said. "We had never heard of this approach for Nrf2 activation and immediately agreed to initiate this collaborative effort that led to the generation of great data and this publication."

This partnership underscores the importance of interdisciplinary research in developing new therapeutic modalities.

Impact

With the development of this innovative technology, Gianneschi and his colleagues at the International Institute for Nanotechnology and the Johnson Lab at the University of Wisconsin-Madison, are not just advancing the field of medicinal chemistry, they are opening new pathways to combat some of the most challenging and devastating neurodegenerative diseases faced by society today. As this research progresses towards clinical application, it may soon offer new hope to those suffering from diseases of oxidative stress such as Alzheimer's and Parkinson's diseases.

"By controlling materials at the scale of single nanometers, we're opening new possibilities in the fight against diseases that are more prevalent than ever, yet remain untreatable," Gianneschi said. "This study is just the beginning. We're excited about the possibilities as we continue to explore and expand the development of macromolecular drugs, capable of mimicking some of the aspects of proteins using our PLP platform."

Join Redox Medicine 2024 this June in Paris, where we will cover all new insights into redox medicine and neurodegenerative diseases.

News Source: Northwestern University.

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Renal transplantation stands as a vital therapeutic avenue for individuals grappling with severe chronic kidney diseases. However, a prevailing challenge emerges for younger patients in the form of a scarcity of kidneys procured from donors of comparable age. This often culminates in the transplantation of older organs, elevating the risk of graft rejection and subsequent complications, as compared to older recipients who receive organs from donors of similar age or younger.

A recent paper published in Antioxidants & Redox Signaling Journal delves into this critical issue. The study meticulously examines various senescence biomarkers in both donors and recipients of renal transplants across different age brackets, adhering to the stringent STROBE requirements.

The research, encompassing 61 patients undergoing renal transplant procedures, involved the isolation of blood samples at distinct intervals: 24 hours before the transplant, and at 24 hours, 3 days, 7 days, 3 months, and 6 months post-transplantation. Patients were categorized into three cohorts based on the age relationship between donor and recipient: "Old Donor," "Young Donor," and "Matched."

Key findings underscored a notable increase in mRNA and protein expression of senescence markers, including p16, p21, IL-6, and SASP release, among young patients receiving kidneys from older donors. Conversely, older patients who received kidneys from younger donors exhibited a gradual yet consistent amelioration in their initial senescent profile.

Furthermore, employing a macrophage cell model treated with serum derived from patients six months post-transplant revealed a pro-senescence milieu, presumably orchestrated by the SASP emanating from the patients.

These compelling insights have sparked a hypothesis proposing the potential efficacy of senolytics in curbing the prevalence of senescent cells and alleviating complications associated with the transplantation of older organs in younger recipients.

The study not only sheds light on the intricate interplay between donor age and transplant outcomes but also paves the way for innovative therapeutic strategies aimed at enhancing the efficacy and longevity of renal transplants, particularly for younger recipients.

Join Redox Medicine 2024 this June in Paris, where Dr. Mario Cordero, lead author of the paper, will further elaborate on the relationship between biomarkers and donor age in chronic kidney disease.

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Copyrights: Redox Medicine Society. 

Image Credits: WangXiNa - Freepik.

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The gastrointestinal (GI) barrier serves as the pivotal interface between individuals and their external environment. It consistently contends with the potential for inflammation and oxidative stress stemming from exposure to various foreign agents and microorganisms. Thus, preserving the structural and functional integrity of the GI barrier holds paramount importance for overall health, playing a pivotal role in averting systemic inflammation and oxidative stress, which are significant contributors to age-related ailments. A robust gut ecosystem relies on the maintenance of gut redox homeostasis, a complex interplay of essential elements.

Key determinants of redox homeostasis in the healthy gut (left) and redox dyshomeostasis (right).

According to the paper by Jan Homolak, from the University of Zagreb School of Medicine, Croatia, published in the Biogerontology Journal by Springer, firstly, establishing a foundational electrophilic tone and mucosal gradient is imperative. Secondly, the electrophilic system must possess adequate capacity to produce reactive oxygen species, facilitating efficient elimination of invading microorganisms and prompt restoration of barrier integrity post breaches. These components hinge upon physiological redox signaling mediated by electrophilic pathways such as NOX2 and the H2O2 pathway. Furthermore, the nucleophilic aspect of redox homeostasis should exhibit ample reactivity to rebalance redox levels subsequent to an electrophilic surge. Factors contributing to the nucleophilic arm encompass the availability of reductive substrates and redox signaling facilitated by the cytoprotective Keap1-Nrf2 pathway.

Future investigations should prioritize the identification of preventative and therapeutic interventions aimed at augmenting the resilience and responsiveness of GI redox homeostasis. These endeavors seek to diminish the susceptibility of the gut to detrimental stimuli and counteract the decline in reactivity often witnessed during the aging process. Strengthening GI redox homeostasis holds promise for mitigating the risks associated with age-related gut dysfunctions and optimizing overall healthspan and longevity.

Figure Description:

Intestinal homeostasis is closely interconnected with the gut microbiota, and maintaining a healthy balance contributes to proper physiological redox signaling through the secretion of SCFAs, ROS such as H2O2, PAMPs, and more. On the other hand, maintaining redox homeostasis within the gut epithelium is crucial for preserving a well-balanced microbial community in the intestinal lumen. This is achieved by maintaining a normal electrophilic gradient and facilitating redox signaling in intestinal epithelial cells. The reactivity of epithelial redox homeostasis is sustained by an adequate electrophilic tone, generated by NOX, luminal secretion of DAAO, and other factors. Additionally, activation of the Keap1-Nrf2 pathway plays a vital role in preserving the capacity of the nucleophilic arm of redox homeostasis. The maintenance of redox homeostasis in the intestinal barrier is closely associated with a highly functional gut immune system with efficient immune surveillance mechanisms. DAAO – D-amino acid oxidase; NADPH – nicotinamide adenine dinucleotide phosphate; NOX – NADPH oxidases; SCFAs – short chain fatty acids; RSS – reactive sulfur species; PAMPs – pathogen-associated molecular patterns; GSH – glutathione

Article DOI.

Image Credits: Homolak, J.  Biogerontology 24, 741–752 (2023). 

Researchers from the Center for Translational Immunology at University Medical Center Utrecht (the Netherlands) have identified that a transient inflammatory pain causes mitochondrial and redox changes in sensory neurons that persist beyond pain resolution. These changes appear to predispose to a failure in resolution of pain caused by a subsequent inflammation. Additionally, targeting the cellular redox balance prevents and treats chronic inflammatory pain in rodents.

Pain often persists in patients with an inflammatory disease, even after the inflammation has subsided. The molecular mechanisms leading to this failure in pain resolution and the transition from acute to chronic pain are poorly understood. For some time, there have been clues that mitochondrial dysfunction may be involved. In a clinical study, approximately 70 percent of patients with heritable mitochondrial diseases develop chronic pain. However, the exact role of mitochondria in the resolution of inflammatory pain is unclear.

Mitochondrial disturbances

To unravel the role of mitochondria in pain resolution, Hanneke Willemen PhD in the research group lead by Niels Eijkelkamp PhD (Center for Translational Immunology, UMC Utrecht) used a model of hyperalgesic priming. In this model, a transient inflammation causes neuronal plasticity, which results in persistence of pain after a subsequent inflammatory stimulus; a perfect model to study what goes wrong during pain resolution. Hanneke and co-workers identified that hyperalgesic priming in mice causes mitochondrial and metabolic disturbances in sensory neurons. The investigators associate these disturbances with an increase in the expression of a mitochondrial protein (ATPSc-KMT) which in a previous study has been linked to chronic pain in patients. By using genetic and pharmacological approaches they showed that inhibit mitochondrial respiration, ATPSCKMT expression and supplementation of one of the affected metabolites restores resolution of inflammatory pain and prevents chronic pain development. The results of this study- which was performed with several collaborators, including the University of Oslo (Norway) - have been published this week in Cell Reports Medicine.

Hanneke Willemen concludes: “In our study we provide evidence that a peripheral inflammation induces persistent mitochondrial and metabolic changes in sensory neurons, which affects the ability of neurons to resolve from hyperalgesia induced by a subsequent inflammatory trigger. Thus, metabolic changes in sensory neurons result in failure of endogenous pain resolution pathways and drive the transition to chronic pain. Importantly, targeting mitochondrial respiration, scavenging reactive oxygen species or supplementation with nicotinamide riboside (vitamin B3) both represent potential therapeutic strategies to restore failing pain resolution pathways, thereby treating chronic inflammatory pain.”

Transition to chronic pain

Chronic pain is a leading cause of years lived in disability and impaired quality of life, yet treatment options are limited and often induce severe side effects. The current dogma is that pain resolution is the consequence of the dissipation of the drivers that induced the pain. However, in 12-30 percent of rheumatic arthritis patients pain persists while they have minimal joint inflammation or even are in remission. Accumulating evidence indicates that pain resolution after tissue damage or inflammation is not passive, but rather an active process that involves endogenous pain resolution mechanisms. Failing pain resolution pathways may lead to the transition from acute to chronic pain. Although the molecular mechanisms that contribute to failure in pain resolution are still poorly understood and need unraveling, this study fills a part of this void and identifies a potential therapeutic approach to promote pain resolution.

Source: University Medical Center Utrecht

Photo Credits: Cell Reports Medicine

A recent paper by researchers from University of Buenos Aires was published in the Antioxidants & Redox Signaling (ARS) Journal, sharing groundbreaking insights into the evolving landscape of mitochondrial involvement in immune responses and inflammation. The paper has delved into the multifaceted significance of mitochondria beyond their traditional role in energy management, shedding light on their pivotal contributions to the host immune defense and the pathogenesis of various inflammatory diseases and syndromes.

Significance

The paper underscores the growing importance of mitochondria in the immune response and inflammation, emphasizing the need to unravel diverse mechanisms. Beyond their conventional role, mitochondria play a vital role in the inflammatory response, releasing activation molecules, adapting their structure and function in tandem with the immune response, and serving as a structural foundation for activating intermediates such as the NLRP3 inflammasome.

Critical Issues

Mitochondria's relevance in the immune response spans various levels, encompassing the release of activation molecules, structural and functional adaptations to support immune responses, and acting as a structural base for key intermediates like the NLRP3 inflammasome. The scientific exploration of mitochondrial mechanisms has unveiled intriguing aspects, including the potential involvement of mitochondrial-derived vesicles in preventing uncontrolled situations during the immune response.

Recent Advances

Researchers are continually reassessing the role of mitochondria in acute and chronic inflammation, revealing their crucial roles as central signaling hubs in regulating inflammatory and immune responses. The review presents the current understanding of mitochondrial mechanisms involved, going beyond the well-known concept of mitochondrial dysfunction, to explore their contributions to the onset and development of inflammatory situations.

Future Directions

Mitochondria emerge as a captivating and multifaceted platform for studying and developing pharmaceutical and therapeutic approaches. Ongoing studies are exploring the effects of specific mitochondrial-targeted molecules and treatments aimed at ameliorating the consequences of exacerbated inflammatory components in various pathologies and syndromes. This burgeoning field represents an open area of increasing research interest, promising new avenues for advancing our comprehension and treatment of inflammatory diseases.

Stay tuned for more updates during Redox Medicine 2024 Conference as we navigate the exciting frontier of redox medicine and its intricate connection to the immune response and inflammation.

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