Cell Stress & Chaperones最新文献

{"title":"Multifaceted roles of mammalian heat shock factor 1 in the central nervous system","authors":"Nicholas B. Rozema,&nbsp;Rocio Gomez-Pastor","doi":"10.1016/j.cstres.2025.100109","DOIUrl":"10.1016/j.cstres.2025.100109","url":null,"abstract":"<div><div>Heat shock factor 1 (HSF1) is a stress-protective transcription factor most associated with transcriptional regulation of genes involved thermal stress response and protein folding. The canonical activation cycle of HSF1, in which HSF1 recognizes a simple promoter binding site known as a heat shock element (HSE) to promote the transcription of molecular chaperones, has been well documented. However, it is now evident that mammalian HSF1 exhibits unexpected complexity and participates in the response to a vast array of cellular stress types. The versatility of HSF1 can be attributed to distinct local protein concentrations, posttranslational modifications (PTMs), and binding partners found in different anatomical regions of the mammalian system. Advances in our knowledge of HSF1 under different types of stress have illuminated its vast array of gene targets, ranging from protein folding to mitochondrial homeostasis to cytoskeletal stability and beyond. In this review, we explore current knowledge of mammalian HSF1 and its gene targets within the central nervous system. While HSF1 has been extensively studied in the context of neurodegeneration, our understanding of its diverse roles in this setting remains limited. We also highlight emerging evidence supporting a physiological role for HSF1 in the healthy brain, an area that has received relatively little attention. Advancing a more comprehensive understanding of HSF1 function in the mammalian brain may aid in the development of novel therapeutics aimed at alleviating symptoms across a range of neurological disorders.</div></div>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"30 5","pages":"Article 100109"},"PeriodicalIF":3.2,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144866778","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}

{"title":"Reactive oxygen species in cancer: Mechanistic insights and therapeutic innovations","authors":"Ning Ma ,&nbsp;Yang Wang ,&nbsp;Xin Li ,&nbsp;Meiling Xu ,&nbsp;Dandan Tan","doi":"10.1016/j.cstres.2025.100108","DOIUrl":"10.1016/j.cstres.2025.100108","url":null,"abstract":"<div><div>Reactive oxygen species (ROS), once considered mere metabolic byproducts, are now recognized as crucial elements in the complex behavior of cancer, influencing both its progression and vulnerabilities. In healthy cells, ROS maintains a delicate balance: while small amounts are essential for signaling, excessive quantities can cause damage. Cancer disrupts this equilibrium, leveraging ROS to promote proliferation, metastasis, and survival, while employing antioxidant defenses to prevent self-destruction. It is the balance of ROS that is key to cancer growth: as they initiate cancer-related processes such as Mitogen-Activated Protein Kinase (MAPK), PI3K/Akt, and c-Jun N-terminal Kinase (JNK) pathways, and induce inflammation through NF-κB. Additionally, matrix metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF) break down tissue barriers, fostering a tumor microenvironment (TME) conducive to cancer spread. However, this dependence on ROS presents a dual challenge. The timing, location, and quantity of radical formation, along with the surrounding cellular environment, determine whether ROS facilitate cancer progression or lead to cancer cell death. Disrupting this delicate balance of ROS may reveal new treatment methods, transforming cancer's survival mechanisms into significant weaknesses. This study explores the dual roles of ROS in cancer, examining how their contrasting effects impact tumor growth and revealing unexpected opportunities to shift the balance from growth to vulnerability.</div></div>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"30 5","pages":"Article 100108"},"PeriodicalIF":3.2,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793598","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}

{"title":"Corrigendum to “The protective role of the IRE1α/XBP1 signaling cascade in autophagy during ischemic stress and acute kidney injury” [Cell Stress Chaperones. 2025;30(3):160-171]","authors":"Ting Liu ,&nbsp;Lu Li ,&nbsp;Meixia Meng ,&nbsp;Ming Gao ,&nbsp;Jinhua Zhang ,&nbsp;Yuan Zhang ,&nbsp;Yukun Gan ,&nbsp;Yangjie Dang ,&nbsp;Limin Liu","doi":"10.1016/j.cstres.2025.100094","DOIUrl":"10.1016/j.cstres.2025.100094","url":null,"abstract":"","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"30 5","pages":"Article 100094"},"PeriodicalIF":3.2,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144722548","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}

{"title":"Cytoprotective role of resveratrol in cigarette smoke-induced pyroptosis through Nrf2 pathway activation","authors":"Mengyu Zhang,&nbsp;Chenyang Hu,&nbsp;Guang Yang,&nbsp;Yajie Hu,&nbsp;Yiqing Qu","doi":"10.1016/j.cstres.2025.100107","DOIUrl":"10.1016/j.cstres.2025.100107","url":null,"abstract":"<div><div>Resveratrol, a natural polyphenolic compound, has garnered increasing attention due to its antioxidant and anti-inflammatory properties. In this study, we investigated its protective role against cigarette smoke extract (CSE)-induced pyroptosis in human bronchial epithelial cell lines (BEAS-2B, 16HBE, and A549) and a chronic cigarette smoke (CS)-exposed mouse model. CS exposure is a major pathogenic factor in chronic obstructive pulmonary disease, primarily through promoting oxidative stress, inflammation, and pyroptotic cell death. Our results demonstrate that resveratrol enhances the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway, upregulating downstream antioxidant enzymes such as HO-1 and NQO1. This activation mitigates oxidative stress and inhibits the activation of the TXNIP/NLRP3/caspase-1 inflammasome axis. <em>In vitro</em>, resveratrol reduced ROS accumulation and proinflammatory cytokine release in CSE-stimulated human bronchial epithelial cells. <em>In vivo</em>, resveratrol partially restored lung function and redox homeostasis in CS-exposed mice. Moreover, mechanistic analyses revealed that resveratrol upregulates miR-200a expression, which directly targets Keap1, thereby relieving its inhibition of Nrf2. These findings suggest that resveratrol alleviates CSE-induced pyroptosis by modulating the miR-200a/Keap1/Nrf2 axis and may serve as a potential therapeutic strategy for smoking-related airway diseases. However, additional clinical studies are necessary to confirm its efficacy.</div></div>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"30 5","pages":"Article 100107"},"PeriodicalIF":3.2,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144759201","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}

{"title":"In vivo imaging of heat shock protein 90: Diagnostic tool and support for Hsp90-targeted therapy","authors":"Romy Cools ,&nbsp;Koen Vermeulen ,&nbsp;Guy Bormans","doi":"10.1016/j.cstres.2025.100105","DOIUrl":"10.1016/j.cstres.2025.100105","url":null,"abstract":"<div><div>The molecular chaperone heat shock protein 90 (Hsp90), essential for protein homeostasis and cellular stress response, has emerged as a promising therapeutic target across various diseases, including cancer, neurodegenerative disorders, and inflammatory conditions. Although numerous Hsp90 inhibitors have been developed and extensively evaluated in clinical studies, progress has been impeded by limited clinical efficacy, narrow therapeutic windows, and challenges in assessing target engagement. These limitations highlight the importance of developing complementary noninvasive molecular imaging tools to better understand Hsp90 function <em>in vivo</em> and optimize therapeutic strategies, including assessing target engagement, refining dosing strategies, monitoring treatment response, and enabling patient stratification. This review provides a comprehensive overview of the current landscape of Hsp90-targeted molecular imaging. We discuss imaging modalities applicable to Hsp90, optical imaging, single-photon emission computed tomography, and positron emission tomography, and highlight key molecular probes developed to visualize Hsp90 expression and function <em>in vivo</em> using these modalities. Furthermore, we summarize significant findings that have deepened our fundamental understanding of Hsp90’s role in disease, supported the development of novel therapeutic approaches, demonstrated imaging effectiveness in preclinical models, and suggested potential for integration into clinical research. We also address current challenges and propose future directions for the field. Through this review, we aim to illustrate the translational potential of molecular imaging in advancing our understanding of Hsp90 in disease and optimizing Hsp90-targeted therapeutics, thereby contributing to precision medicine approaches.</div></div>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"30 5","pages":"Article 100105"},"PeriodicalIF":3.2,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728276","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}

{"title":"Gangliosides and cholesterol, two major components of the membrane lipid rafts, as new regulatory partners for stress granules assembly","authors":"Anaïs Aulas,&nbsp;Coralie Di Scala","doi":"10.1016/j.cstres.2025.100093","DOIUrl":"10.1016/j.cstres.2025.100093","url":null,"abstract":"<div><div>Stress granules are cytoplasmic inclusions with cyto-protective functions assembling in response to stress. They are now accepted to be part of the pathological mechanism in several diseases, from cancer to neurodegenerative disorders. However, the field is still struggling to find common regulators of their assembly and function. In this study, we describe a mechanism involving lipid rafts (gangliosides and cholesterol), in the regulation of stress granules formation. This study reports that membrane lipid composition is able to regulate the formation of stress granules potentially unraveling several disease mechanisms.</div></div>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"30 5","pages":"Article 100093"},"PeriodicalIF":3.2,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682110","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}

{"title":"Heat-induced phosphatidylserine changes drive HSPA1A's plasma membrane localization","authors":"Jensen Low ,&nbsp;Rachel Altman ,&nbsp;Allen Badolian ,&nbsp;Azalea Blythe Cuaresma ,&nbsp;Carolina Briseño ,&nbsp;Uri Keshet ,&nbsp;Oliver Fiehn ,&nbsp;Robert V. Stahelin ,&nbsp;Nikolas Nikolaidis","doi":"10.1016/j.cstres.2025.100092","DOIUrl":"10.1016/j.cstres.2025.100092","url":null,"abstract":"<div><div>HSPA1A is a molecular chaperone crucial in cell survival. In addition to its cytosolic functions, HSPA1A translocates to heat-shocked and cancer cells' plasma membrane (PM). In cancer, PM-localized HSPA1A (mHSPA1A) is associated with increased tumor aggressiveness and therapeutic resistance, suggesting that preventing its membrane localization could have therapeutic value. This translocation depends on HSPA1A's interaction with PM phospholipids, including phosphatidylserine (PS). Although PS binding regulates HSPA1A's membrane localization, the exact trigger for this movement remains unclear. Given that lipid modifications are a cancer hallmark, we hypothesized that PS is a crucial lipid driving HSPA1A translocation and that heat-induced changes in PS levels trigger HSPA1A's PM localization in response to heat stress. We tested this hypothesis using pharmacological inhibition and RNA interference targeting PS synthesis, combined with confocal microscopy, lipidomics, and western blotting. Lipidomic analysis and PS-specific biosensors confirmed a heat shock-induced PS increase, peaking immediately post-stress. Inhibition of PS synthesis with fendiline and RNA interference significantly reduced HSPA1A's PM localization, while depletion of cholesterol or fatty acids had minimal effects, confirming specificity for PS. Further experiments showed that PS saturation and elongation changes did not significantly impact HSPA1A's PM localization, indicating that the total PS increase, rather than specific PS species, is the critical factor. These findings reshape current models of HSPA1A trafficking, demonstrating that PS is a crucial regulator of HSPA1A's membrane translocation during the heat shock response. This work offers new insights into lipid-regulated protein trafficking and highlights the importance of PS in controlling cellular responses to stress.</div></div>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"30 5","pages":"Article 100092"},"PeriodicalIF":3.3,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144625463","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}

{"title":"HSPA2 emerges as a key biomarker: Insights from global lysine acetylproteomic profiling in idiopathic male infertility","authors":"Lisa Goutami ,&nbsp;Soumya Ranjan Jena ,&nbsp;Ajaya Kumar Moharana ,&nbsp;Anwesha Pradhan ,&nbsp;Sujata Kar ,&nbsp;Luna Samanta","doi":"10.1016/j.cstres.2025.100090","DOIUrl":"10.1016/j.cstres.2025.100090","url":null,"abstract":"<div><div>Spermatozoa are highly specialized cells, and any alterations in their protein profiles may affect their function and fertilizing ability. In spermatozoa, which are transcriptionally and translationally inactive, molecular chaperones, particularly heat shock proteins, play crucial roles in maintaining redox balance and preserving protein integrity. Post-translational modifications, particularly lysine acetylation, influence chaperone function and are lately being recognized in the pathophysiology of male infertility. To assess the impact of lysine acetylation on sperm chaperone proteins in idiopathic infertile patients (IIP) compared to fertile donors (FD), we performed immunoprecipitation coupled with liquid chromatography and tandam mass spectroscpy analysis of lysine acetylated sperm proteins from both groups. Proteomic analysis revealed 2988 acetylated proteins, comprising 26 chaperone proteins that were differentially expressed, with four upregulated and nine downregulated in the IIP group. Functional analyses demonstrated enrichment of these proteins in protein folding, spermatogenesis, and response to oxidative stress. CytoHubba analysis reported key HSP70 family members, HSPA2, HSPA4, and HSPA1A as central hub proteins in protein–protein interaction networks. STRING and Ingenuity Pathway Analysis (IPA) network analyses further highlighted the central regulatory roles of these chaperones, with HSPA2 emerging as a key hub protein based on friendship analysis. Western blot validation revealed hypoacetylation and downregulation of HSPA2 in spermatozoa from the IIP group, accompanied by elevated levels of 4-Hydroxynonenal (4-HNE), indicating a link between redox imbalance and altered lysine acetylation in chaperone proteins. Additionally, intense aniline blue staining of sperm nuclei in the IIP group suggested aberrant spermiogenesis. Considering HSPA2′s well-documented involvement in sperm maturation and oocyte recognition, its diminished acetylation and expression may not only act as a potential biomarker but also contribute mechanistically to the development of idiopathic male infertility. This study underscores the significance of lysine acetylation in HSPA2 in regulating chaperone function and highlights its diagnostic and therapeutic potential in unexplained male infertility.</div></div>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"30 5","pages":"Article 100090"},"PeriodicalIF":3.2,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144616472","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}

{"title":"Combined approaches to reduce stress and improve livestock well-being: A review","authors":"Ariel Shabtay","doi":"10.1016/j.cstres.2025.100091","DOIUrl":"10.1016/j.cstres.2025.100091","url":null,"abstract":"<div><div>It is well established that various stressors confer hazardous impact on the welfare, health, productive, and reproductive efficiencies of farm animals. Among the major stress stimuli, temperature, transportation, weaning, pathogens, diet quality, and routine handling are cardinal in causing diminished performance of livestock. It is hypothesized that the key to reducing disease incidence and animal discomfort appears to be centered at reducing their response to stress. To this end, strategies that involve thermal conditioning at an early age, dietary interventions, and identification of genetic and biochemical biomarkers to predict the risk for developing stress-related diseases an early, have been studied by our research team during the last two decades as means to alleviate stress in Aves and ruminants. The findings from these studies are presented here to illustrate how the applied strategies have contributed to the following outcomes: 1. In layer hens: Improved regulation of body temperature, reduced mortality rates, and a delayed onset of heat shock protein induction. 2. In cattle: a. mitigation of intestinal diseases and prevention of blood parasite invasion; b. identification of genomic and proteomic biomarkers predictive of susceptibility to bovine respiratory disease, the leading cause of morbidity and mortality among young cattle globally.</div></div>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"30 5","pages":"Article 100091"},"PeriodicalIF":3.3,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144616471","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}

{"title":"Editorial Board Members/Copyright","authors":"","doi":"10.1016/S1355-8145(25)00043-4","DOIUrl":"10.1016/S1355-8145(25)00043-4","url":null,"abstract":"","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"30 4","pages":"Article 100098"},"PeriodicalIF":3.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144686614","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}