Pub Date : 2025-12-16DOI: 10.1016/j.cstres.2025.100139
Claes Andréasson , Anat Ben-Zvi
Cells safeguard the functionality of the proteome using complex pathways of protein quality control. The centerpiece of this proteostasis network is a large set of molecular chaperones and proteases that impact the entire lifespan of proteins by controlling protein folding and degradation. Dysfunction of the proteostasis network is associated with many diseases and age-associated functional decline of neurons, including Alzheimer’s and Parkinson’s diseases, as well as several motor neuron diseases. The 2025 EMBO workshop “Protein quality control: from molecular mechanisms to aging and disease” gathered the large and interdisciplinary community of researchers that study protein quality control, from its fundamental molecular mechanisms via higher-order organization in organisms to its impact on and use in the medical field. Here we summarize the workshop and report research findings.
{"title":"Protein quality control: From molecular mechanisms to aging and disease—EMBO workshop, May 18-23, 2025, Hersonissos, Greece","authors":"Claes Andréasson , Anat Ben-Zvi","doi":"10.1016/j.cstres.2025.100139","DOIUrl":"10.1016/j.cstres.2025.100139","url":null,"abstract":"<div><div>Cells safeguard the functionality of the proteome using complex pathways of protein quality control. The centerpiece of this proteostasis network is a large set of molecular chaperones and proteases that impact the entire lifespan of proteins by controlling protein folding and degradation. Dysfunction of the proteostasis network is associated with many diseases and age-associated functional decline of neurons, including Alzheimer’s and Parkinson’s diseases, as well as several motor neuron diseases. The 2025 EMBO workshop “Protein quality control: from molecular mechanisms to aging and disease” gathered the large and interdisciplinary community of researchers that study protein quality control, from its fundamental molecular mechanisms via higher-order organization in organisms to its impact on and use in the medical field. Here we summarize the workshop and report research findings.</div></div>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"31 1","pages":"Article 100139"},"PeriodicalIF":3.2,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145780388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-03DOI: 10.1016/j.cstres.2025.100131
Xavier Jeanne , Jasmeen Oberoi , Mark S. Roe , Matthias Baud , John Spencer , Zsolt Torok , Laszlo Vigh , Chrisostomos Prodromou
LA1011 (dimethyl 4-(4-Trifluoro-methyl-phenyl)-2,6-bis(2-dimethylamino-ethyl)-1-methyl-1-4 dihydropyridine-3-5-dicarboxylate dihydrochloride) has been shown to improve the prognosis of Alzheimer’s disease (AD) in an APPxPS1 mouse model. The target for LA1011 is the C-terminal domain of Hsp90, where it was shown previously to reduce the interaction between FKBP51 and Hsp90. FKBP51 is a Hsp90 co-chaperone that promotes the trans to cis isomerization of proline at multiple tau pSer/pThr-pro sites, thus preventing their dephosphorylation. Potentially this leads to the hyperphosphorylation of tau and the formation of neurofibrillary tangles that eventually lead to the development of AD. In this study, we demonstrate that LA1011 affects the FKBP51-mediated regulation of Hsp90 but also potentially modulates the regulation Hsp90 by the co-chaperones FKBP52, CHIP, Aha1, Hch1 and PP5. We also show that the co-chaperones HOP, CDC37 and Sgt1 appear to enhance mildly the binding of LA1011. In contrast, nucleotide alone or nucleotide with Aha1 or p23, which promote the closed conformation of Hsp90, reduce the affinity for LA1011. We conclude that LA1011 can modulate the regulatory landscape of the Hsp90 co-chaperone network, which in turn appears to improve the prognosis of Alzheimer’s disease.
{"title":"The dihydropyridine LA1011 modulates multiple Hsp90—co-chaperone interactions relevant to Alzheimer’s disease","authors":"Xavier Jeanne , Jasmeen Oberoi , Mark S. Roe , Matthias Baud , John Spencer , Zsolt Torok , Laszlo Vigh , Chrisostomos Prodromou","doi":"10.1016/j.cstres.2025.100131","DOIUrl":"10.1016/j.cstres.2025.100131","url":null,"abstract":"<div><div>LA1011 (dimethyl 4-(4-Trifluoro-methyl-phenyl)-2,6-bis(2-dimethylamino-ethyl)-1-methyl-1-4 dihydropyridine-3-5-dicarboxylate dihydrochloride) has been shown to improve the prognosis of Alzheimer’s disease (AD) in an APPxPS1 mouse model. The target for LA1011 is the C-terminal domain of Hsp90, where it was shown previously to reduce the interaction between FKBP51 and Hsp90. FKBP51 is a Hsp90 co-chaperone that promotes the <em>trans</em> to <em>cis</em> isomerization of proline at multiple tau pSer/pThr-pro sites, thus preventing their dephosphorylation. Potentially this leads to the hyperphosphorylation of tau and the formation of neurofibrillary tangles that eventually lead to the development of AD. In this study, we demonstrate that LA1011 affects the FKBP51-mediated regulation of Hsp90 but also potentially modulates the regulation Hsp90 by the co-chaperones FKBP52, CHIP, Aha1, Hch1 and PP5. We also show that the co-chaperones HOP, CDC37 and Sgt1 appear to enhance mildly the binding of LA1011. In contrast, nucleotide alone or nucleotide with Aha1 or p23, which promote the closed conformation of Hsp90, reduce the affinity for LA1011. We conclude that LA1011 can modulate the regulatory landscape of the Hsp90 co-chaperone network, which in turn appears to improve the prognosis of Alzheimer’s disease.</div></div>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"31 1","pages":"Article 100131"},"PeriodicalIF":3.2,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145687170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.cstres.2025.100129
Sarah J. Backe , Dimitra Bourboulia , Mark R. Woodford , Mehdi Mollapour
Heat shock protein 90 (Hsp90) stabilizes numerous oncogenic proteins, making it a key therapeutic target in cancer. This protocol details an ex vivo method using freshly resected human renal cell carcinoma tissues to evaluate fluorescently labeled Hsp90 inhibitor ganetespib accumulation in tumor versus normal tissue. By preserving the native tumor architecture, this method offers a physiologically relevant alternative to xenograft models. This protocol combines flow cytometry and confocal microscopy to quantitatively and visually assess ganetespib uptake, providing insight into drug distribution and therapeutic response in human cancers. For complete details on the use and execution of this protocol, please refer to Dunn et al. and Woodford et al.
{"title":"Ex vivo qualitative and quantitative analysis of fluorescently-labeled Hsp90 drug in human tumors","authors":"Sarah J. Backe , Dimitra Bourboulia , Mark R. Woodford , Mehdi Mollapour","doi":"10.1016/j.cstres.2025.100129","DOIUrl":"10.1016/j.cstres.2025.100129","url":null,"abstract":"<div><div>Heat shock protein 90 (Hsp90) stabilizes numerous oncogenic proteins, making it a key therapeutic target in cancer. This protocol details an <em>ex vivo</em> method using freshly resected human renal cell carcinoma tissues to evaluate fluorescently labeled Hsp90 inhibitor ganetespib accumulation in tumor versus normal tissue. By preserving the native tumor architecture, this method offers a physiologically relevant alternative to xenograft models. This protocol combines flow cytometry and confocal microscopy to quantitatively and visually assess ganetespib uptake, providing insight into drug distribution and therapeutic response in human cancers. For complete details on the use and execution of this protocol, please refer to Dunn et al. and Woodford et al.</div></div>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"30 6","pages":"Article 100129"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145630397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-26DOI: 10.1016/j.cstres.2025.100130
Alberto Arce , Rachel Altman , Allen Badolian , Jensen Low , Azalea Blythe Cuaresma , Georgia Halkia , Uri Keshet , Oliver Fiehn , Robert V. Stahelin , Nikolas Nikolaidis
Heat shock protein A1A (HSPA1A), a major heat shock (HS) protein, is known to translocate to the plasma membrane (PM) in response to cellular stress and cancer, where it plays protective roles in membrane integrity and stress resistance. Although phosphatidylinositol 4-phosphate [PI(4)P] is essential in this translocation, the signals that trigger and facilitate HSPA1A's movement remain undefined. Given that membrane lipid composition dynamically shifts during stress, we hypothesized that HS-induced PI(4)P changes are crucial for HSPA1A's PM localization. To test this hypothesis, we investigated the mechanisms driving PI(4)P changes and HSPA1A PM localization under HS. Lipidomic analysis, enzyme-linked immunosorbent assay (ELISA), and confocal imaging revealed a rapid PI(4)P increase at the PM post-HS, with levels peaking immediately after HS (0 h recovery) and declining by 8 h of recovery. RNA sequencing and protein quantification indicated no transcriptional increase in PI4KIII alpha, the kinase responsible for PI(4)P synthesis, suggesting an alternative regulatory mechanism. Hypothesizing that HS enhances PI4KIII alpha activity, we performed ELISA coupled with immunoprecipitation, confirming a significant rise in PI4KIII alpha activity following HS. Functional analyses further demonstrated that RNAi-mediated PI4KIII alpha depletion or pharmacological PI(4)P reduction, using GSK-A1, impairs HSPA1A's localization to the PM, confirming that HSPA1A translocation is PI(4)P-dependent. Our findings identify PI4KIII alpha activity as a key regulator of PI(4)P accumulation and subsequent HSPA1A recruitment to the PM in stressed and cancer cells. This lipid-mediated response offers new insights into stress adaptation and potentially modifiable pathways for therapeutic interventions to control HSPA1A function in cancer.
{"title":"Heat shock-induced PI(4)P increase drives HSPA1A translocation to the plasma membrane in cancer and stressed cells through PI4KIII alpha activation","authors":"Alberto Arce , Rachel Altman , Allen Badolian , Jensen Low , Azalea Blythe Cuaresma , Georgia Halkia , Uri Keshet , Oliver Fiehn , Robert V. Stahelin , Nikolas Nikolaidis","doi":"10.1016/j.cstres.2025.100130","DOIUrl":"10.1016/j.cstres.2025.100130","url":null,"abstract":"<div><div>Heat shock protein A1A (HSPA1A), a major heat shock (HS) protein, is known to translocate to the plasma membrane (PM) in response to cellular stress and cancer, where it plays protective roles in membrane integrity and stress resistance. Although phosphatidylinositol 4-phosphate [PI(4)P] is essential in this translocation, the signals that trigger and facilitate HSPA1A's movement remain undefined. Given that membrane lipid composition dynamically shifts during stress, we hypothesized that HS-induced PI(4)P changes are crucial for HSPA1A's PM localization. To test this hypothesis, we investigated the mechanisms driving PI(4)P changes and HSPA1A PM localization under HS. Lipidomic analysis, enzyme-linked immunosorbent assay (ELISA), and confocal imaging revealed a rapid PI(4)P increase at the PM post-HS, with levels peaking immediately after HS (0 h recovery) and declining by 8 h of recovery. RNA sequencing and protein quantification indicated no transcriptional increase in PI4KIII alpha, the kinase responsible for PI(4)P synthesis, suggesting an alternative regulatory mechanism. Hypothesizing that HS enhances PI4KIII alpha activity, we performed ELISA coupled with immunoprecipitation, confirming a significant rise in PI4KIII alpha activity following HS. Functional analyses further demonstrated that RNAi-mediated PI4KIII alpha depletion or pharmacological PI(4)P reduction, using GSK-A1, impairs HSPA1A's localization to the PM, confirming that HSPA1A translocation is PI(4)P-dependent. Our findings identify PI4KIII alpha activity as a key regulator of PI(4)P accumulation and subsequent HSPA1A recruitment to the PM in stressed and cancer cells. This lipid-mediated response offers new insights into stress adaptation and potentially modifiable pathways for therapeutic interventions to control HSPA1A function in cancer.</div></div>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"31 1","pages":"Article 100130"},"PeriodicalIF":3.2,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145630392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-03DOI: 10.1016/j.cstres.2025.100128
Wael M. Elshemey , Hamdy I.A. Mostafa , Abdo A. Elfiky
Human Immuno-deficiency virus (HIV) is still spreading all over the world. There are many routes through which the virus recognizes host cells by its envelope protein. One of these routes is through binding to glucose-regulated protein 78 (GRP78), which is overexpressed in stressed cells. In this study, we investigate the association between GRP78 and HIV envelope protein at four different binding sites (R1: C130-C162), (R2: C223-C252), (R3: C301-C335), and (R4: C388-C418) using a comprehensive in silico approach. Protein-protein docking and molecular dynamics simulations (MDS) are conducted to evaluate the binding. Results indicate that the R4 region (C388-C418) is the potential binding site of the envelope protein to GRP78 on the cell surface with an average binding energy of −12.20 ± 2.0 kcal/mol. The predicted findings open the gate towards further studies that could lead to the development of effective inhibitors that can alleviate viral recognition of the host cell and eradicate the viral infection.
{"title":"Computational characterization of HIV envelope interactions with cellular GRP78 as a potential entry mechanism","authors":"Wael M. Elshemey , Hamdy I.A. Mostafa , Abdo A. Elfiky","doi":"10.1016/j.cstres.2025.100128","DOIUrl":"10.1016/j.cstres.2025.100128","url":null,"abstract":"<div><div>Human Immuno-deficiency virus (HIV) is still spreading all over the world. There are many routes through which the virus recognizes host cells by its envelope protein. One of these routes is through binding to glucose-regulated protein 78 (GRP78), which is overexpressed in stressed cells. In this study, we investigate the association between GRP78 and HIV envelope protein at four different binding sites (R1: C130-C162), (R2: C223-C252), (R3: C301-C335), and (R4: C388-C418) using a comprehensive <em>in silico</em> approach. Protein-protein docking and molecular dynamics simulations (MDS) are conducted to evaluate the binding. Results indicate that the R4 region (C388-C418) is the potential binding site of the envelope protein to GRP78 on the cell surface with an average binding energy of −12.20 ± 2.0 kcal/mol. The predicted findings open the gate towards further studies that could lead to the development of effective inhibitors that can alleviate viral recognition of the host cell and eradicate the viral infection.</div></div>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"30 6","pages":"Article 100128"},"PeriodicalIF":3.2,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145450757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
As the global demographics shifts towards an increasingly aging population, understanding the effects and molecular mechanisms underlying aging becomes more and more important within biomedical research. A hallmark of aging is the progressive deterioration of protein homeostasis (proteostasis), characterized by the accumulation of misfolded protein aggregates within the cell. The proteostasis network is essential in mitigating the harmful effects of proteotoxic aggregates by activating stress response and degradation pathways. Significant discoveries in aging research are often inherently intertwined with proteostasis, many of which were made using the invertebrate Caenorhabditis elegans. Many longevity pathways, such as the insulin-like signaling pathway, initially identified in C. elegans, are mediated through inter-tissue stress signaling from the nervous system, intestine, or gonad. These cell nonautonomous signaling pathways not only enhance lifespan and stress resilience but also limit age-related accumulation of protein aggregates that exacerbate age-associated diseases. Thus, findings from aging research were often key to providing new insights into cell nonautonomous regulation of stress responses and organismal proteostasis. In this review, we outline key discoveries made using C. elegans as a model system and highlight their contributions that led to our current understanding of inter-tissue communication in organismal proteostasis regulation. We furthermore highlight emerging concepts and discuss the translational relevance of conserved cell nonautonomous proteostasis regulation in mammals. We emphasize the importance of mammalian research to support the research done in C. elegans, with the future goal of developing potential therapeutic interventions targeting these inter-tissue proteostasis signaling pathways to combat aging.
{"title":"Signal relay in C. elegans: A tissue-perspective on coordinating organismal proteostasis and its impact on aging","authors":"Loren Cocciolone, Akhil Souparnika, Valeria Uvarova, Katie Kessler, Patricija van Oosten-Hawle","doi":"10.1016/j.cstres.2025.100127","DOIUrl":"10.1016/j.cstres.2025.100127","url":null,"abstract":"<div><div>As the global demographics shifts towards an increasingly aging population, understanding the effects and molecular mechanisms underlying aging becomes more and more important within biomedical research. A hallmark of aging is the progressive deterioration of protein homeostasis (proteostasis), characterized by the accumulation of misfolded protein aggregates within the cell. The proteostasis network is essential in mitigating the harmful effects of proteotoxic aggregates by activating stress response and degradation pathways. Significant discoveries in aging research are often inherently intertwined with proteostasis, many of which were made using the invertebrate <em>Caenorhabditis elegans</em>. Many longevity pathways, such as the insulin-like signaling pathway, initially identified in <em>C. elegans,</em> are mediated through inter-tissue stress signaling from the nervous system, intestine, or gonad. These cell nonautonomous signaling pathways not only enhance lifespan and stress resilience but also limit age-related accumulation of protein aggregates that exacerbate age-associated diseases. Thus, findings from aging research were often key to providing new insights into cell nonautonomous regulation of stress responses and organismal proteostasis. In this review, we outline key discoveries made using <em>C. elegans</em> as a model system and highlight their contributions that led to our current understanding of inter-tissue communication in organismal proteostasis regulation. We furthermore highlight emerging concepts and discuss the translational relevance of conserved cell nonautonomous proteostasis regulation in mammals. We emphasize the importance of mammalian research to support the research done in <em>C. elegans,</em> with the future goal of developing potential therapeutic interventions targeting these inter-tissue proteostasis signaling pathways to combat aging.</div></div>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"30 6","pages":"Article 100127"},"PeriodicalIF":3.2,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145336508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-17DOI: 10.1016/j.cstres.2025.100126
Carol Nguyen , Rafael Ishihara Figueiroa , Cristiano Mendes da Silva , Elaine Hatanaka , Gary Sweeney , Rafael Herling Lambertucci
Introduction
Diabetes mellitus affects millions of people worldwide and there is evidence linking the increase of oxidative stress to the development of diabetic cardiomyopathy. Melatonin has been found to possess powerful antioxidant properties via modulating both enzymatic and non-enzymatic antioxidant systems.
Objective
To evaluate the antioxidant potential of melatonin on the heart of diabetic animals at basal conditions and following 2 h of strenuous exercise.
Methods
Diabetic animals were divided into two groups: non-supplemented and supplemented (melatonin). We evaluated oxidative stress biomarkers, total glutathione amount, oxidative stress index and antioxidant enzymes mRNA expression, immediately after an exhaustive exercise (IA group), and 2 h after exhausted exercise (2 h group). We also included a non-exercised group (0 h).
Results
Comparing to non-exercised animals, exercise immediately induced an increase of nitrite and total antioxidant status in non-supplemented and supplemented animals, respectively. In melatonin-supplemented animals, the oxidative stress index decreased immediately after exercise (IA group) compared to non-exercised animals (0 h), an effect not seen in the non-supplemented group. Compared to non-supplemented, melatonin supplementation was shown to attenuate TBARS at all time points and increase total glutathione content at times 0 h and IA. mRNA expression of some antioxidant enzymes (CAT and GPX) was modulated by melatonin, especially when associated with exercise [catalase (CAT) and Cu, Zn superoxide dismutase (SOD)].
Conclusion
Our findings demonstrate that melatonin confers antioxidant protection to the diabetic heart, primarily by increasing glutathione levels and attenuating lipid peroxidation. This establishes a protective state that enhances cardiac resilience, and the combination of melatonin and exercise may offer synergistic benefits against acute, stress-induced oxidative damage in diabetic animals.
{"title":"Melatonin attenuates cardiac oxidative stress in diabetic rats following acute exhaustive exercise","authors":"Carol Nguyen , Rafael Ishihara Figueiroa , Cristiano Mendes da Silva , Elaine Hatanaka , Gary Sweeney , Rafael Herling Lambertucci","doi":"10.1016/j.cstres.2025.100126","DOIUrl":"10.1016/j.cstres.2025.100126","url":null,"abstract":"<div><h3>Introduction</h3><div>Diabetes mellitus affects millions of people worldwide and there is evidence linking the increase of oxidative stress to the development of diabetic cardiomyopathy. Melatonin has been found to possess powerful antioxidant properties <em>via</em> modulating both enzymatic and non-enzymatic antioxidant systems.</div></div><div><h3>Objective</h3><div>To evaluate the antioxidant potential of melatonin on the heart of diabetic animals at basal conditions and following 2 h of strenuous exercise.</div></div><div><h3>Methods</h3><div>Diabetic animals were divided into two groups: non-supplemented and supplemented (melatonin). We evaluated oxidative stress biomarkers, total glutathione amount, oxidative stress index and antioxidant enzymes mRNA expression, immediately after an exhaustive exercise (IA group), and 2 h after exhausted exercise (2 h group). We also included a non-exercised group (0 h).</div></div><div><h3>Results</h3><div>Comparing to non-exercised animals, exercise immediately induced an increase of nitrite and total antioxidant status in non-supplemented and supplemented animals, respectively. In melatonin-supplemented animals, the oxidative stress index decreased immediately after exercise (IA group) compared to non-exercised animals (0 h), an effect not seen in the non-supplemented group. Compared to non-supplemented, melatonin supplementation was shown to attenuate TBARS at all time points and increase total glutathione content at times 0 h and IA. mRNA expression of some antioxidant enzymes (CAT and GPX) was modulated by melatonin, especially when associated with exercise [catalase (CAT) and Cu, Zn superoxide dismutase (SOD)].</div></div><div><h3>Conclusion</h3><div>Our findings demonstrate that melatonin confers antioxidant protection to the diabetic heart, primarily by increasing glutathione levels and attenuating lipid peroxidation. This establishes a protective state that enhances cardiac resilience, and the combination of melatonin and exercise may offer synergistic benefits against acute, stress-induced oxidative damage in diabetic animals.</div></div>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"30 6","pages":"Article 100126"},"PeriodicalIF":3.2,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145328419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Candida albicans is a fungus that is predominantly detected in the oral cavity and causes opportunistic infections. Among the elderly, a decline in the host's resistance to pathogens due to immunosenescence makes them more susceptible to oral candidiasis, which eventually may progress to systemic candidiasis. Allyl isothiocyanate (AITC) is a component found in Brassicaceae plants (such as wasabi), which possesses strong antibacterial properties and is used as a food preservative. In this study, the effects of AITC on C. albicans were investigated though: (1) inhibition of growth and biofilm formation, (2) inhibition of adhesion to denture base resin, (3) inhibition of dimorphic transformation that exacerbates pathogenicity, and (4) inhibition of the production of secretory aspartic protease and lipase. Taken together, this suggests that AITC suppresses the growth and pathogenicity of this fungus. Further investigation of the mechanism revealed a decrease in hyphae-specific gene expression in the intracellular signaling MAP kinase cascade and cAMP pathway, as well as the induction of oxidative stress and a tendency toward apoptosis within C. albicans cells. Based on these findings, we propose that AITC may be beneficial for the prevention and suppression of oral candidiasis and has the potential for clinical application aimed at improving oral care and quality of life.
{"title":"Allyl isothiocyanate suppresses the growth and pathogenicity of Candida albicans","authors":"Hideki Nishiura , Muneaki Tamura , Rieko Matsuike , Marni C. Cueno , Tomoka Ito , Yasuhiro Namura , Toshimitsu Iinuma , Kenichi Imai","doi":"10.1016/j.cstres.2025.100125","DOIUrl":"10.1016/j.cstres.2025.100125","url":null,"abstract":"<div><div><em>Candida albicans</em> is a fungus that is predominantly detected in the oral cavity and causes opportunistic infections. Among the elderly, a decline in the host's resistance to pathogens due to immunosenescence makes them more susceptible to oral candidiasis, which eventually may progress to systemic candidiasis. Allyl isothiocyanate (AITC) is a component found in Brassicaceae plants (such as wasabi), which possesses strong antibacterial properties and is used as a food preservative. In this study, the effects of AITC on <em>C. albicans</em> were investigated though: (1) inhibition of growth and biofilm formation, (2) inhibition of adhesion to denture base resin, (3) inhibition of dimorphic transformation that exacerbates pathogenicity, and (4) inhibition of the production of secretory aspartic protease and lipase. Taken together, this suggests that AITC suppresses the growth and pathogenicity of this fungus. Further investigation of the mechanism revealed a decrease in hyphae-specific gene expression in the intracellular signaling MAP kinase cascade and cAMP pathway, as well as the induction of oxidative stress and a tendency toward apoptosis within <em>C. albicans</em> cells. Based on these findings, we propose that AITC may be beneficial for the prevention and suppression of oral candidiasis and has the potential for clinical application aimed at improving oral care and quality of life.</div></div>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"30 6","pages":"Article 100125"},"PeriodicalIF":3.2,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145273970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号