{"title":"Therapeutic applications of exercise in neurodegenerative diseases: focusing on the mechanism of SIRT1.","authors":"Jingwen Li, Tingting Liu, Meiyan Xian, Jianshe Wei","doi":"10.1007/s11010-025-05299-8","DOIUrl":"10.1007/s11010-025-05299-8","url":null,"abstract":"<p><p>Neurodegenerative diseases comprise a group of central nervous system disorders marked by progressive neuronal degeneration and dysfunction. Their pathogenesis is multifactorial, involving oxidative stress, mitochondrial dysfunction, excitotoxicity, and neuroinflammation. Recent research has highlighted the potential of exercise as a non-pharmacological intervention for both the prevention and treatment of these disorders. In particular, exercise has received growing attention for its capacity to upregulate the expression and activity of SIRT1, a critical mediator of neuroprotection via downstream signaling pathways. SIRT1, a key member of the Sirtuin family, is a nicotinamide adenine dinucleotide (NAD +)-dependent class III histone deacetylase. It plays an essential role in regulating cellular metabolism, energy homeostasis, gene expression, and cellular longevity. In the context of neurodegenerative diseases, SIRT1 confers neuroprotection by modulating multiple signaling cascades through deacetylation, suppressing neuronal apoptosis, and promoting neural repair and regeneration. Exercise enhances SIRT1 expression and activity by increasing NAD + synthesis and utilization, improving intracellular redox balance, alleviating oxidative stress-induced inhibition of SIRT1, and thereby promoting its activation. Moreover, exercise may indirectly modulate SIRT1 function by influencing interacting molecular networks. This review summarizes recent advances in the therapeutic application of exercise for neurodegenerative diseases, with a focus on SIRT1 as a central mechanism. It examines how exercise mediates neuroprotection through the regulation of SIRT1 and its associated molecular mechanisms and signaling pathways. Finally, the paper discusses the potential applications and challenges of integrating exercise and SIRT1-targeted strategies in the management of neurodegenerative diseases, offering novel perspectives for the development of innovative treatments and improvements in patients' quality of life.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"4921-4939"},"PeriodicalIF":3.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144002026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Disease-modifying effect of donepezil on APP/PS1 mice at different stages of Alzheimer's disease.","authors":"Irina Zueva, Grigory Belyaev, Konstantin Petrov","doi":"10.1007/s11010-025-05310-2","DOIUrl":"10.1007/s11010-025-05310-2","url":null,"abstract":"<p><p>Despite Alzheimer's disease (AD) representing a significant global health concern, disease-modifying therapeutic options remain elusive. The use of animal models of the disease to develop drugs intended for the treatment of AD does not always predict their efficacy in clinical trials. Our research demonstrates the benefits of a drug-withdrawal approach to screening AD-modifying compounds, focussing on β-amyloid (Aβ)-related pathological changes in APP/PS1 transgenic mice at different stages of the disease. To assess the efficacy of this approach, we examined the AD-modifying effect of donepezil as a reference drug. A significant cognitive decline exhibited by APP/PS1 transgenic mice from 8.4 months of age was accompanied by progressive accumulation of Aβ plaques, decreased synaptophysin and vesicular acetylcholine transporter immunoexpression. Donepezil had a disease-modifying effect, slowing the deterioration of all the pathological markers studied when treatment was started in a pre-symptomatic stage of AD. However, in the group of mice with advanced stage of AD, such disease-modifying effects were not evident.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"5123-5139"},"PeriodicalIF":3.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144120275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Parth Gupta, Devesh Srivastava, Vinayak Nayak, B Vishal Rao, K Suseela, Rakesh Sharma, Senthil J Rajappa, T Subramanyeshwar Rao, Parul Mishra, Ashish Misra
{"title":"YTHDC1 orchestrates oncogenic splicing via the CLK1-SRSF1 splicing machinery to regulate castration-resistant prostate cancer progression.","authors":"Parth Gupta, Devesh Srivastava, Vinayak Nayak, B Vishal Rao, K Suseela, Rakesh Sharma, Senthil J Rajappa, T Subramanyeshwar Rao, Parul Mishra, Ashish Misra","doi":"10.1007/s11010-025-05302-2","DOIUrl":"10.1007/s11010-025-05302-2","url":null,"abstract":"<p><p>Androgen receptor variant 7 (AR-V7) plays a critical role in castration-resistant prostate cancer (CRPC) progression even under androgen-deprivation conditions. Clinical and experimental studies have established that AR-V7 expression is a critical driver of CRPC progression and resistance to first-line anti-androgen therapy including enzalutamide. Understanding the mechanisms regulating AR-V7 generation and its contribution to drug resistance is critical for developing newer approaches to target CRPC. In this study, we have investigated the role of the RNA-binding protein YTHDC1, a m6A reader, in regulating AR-V7 splicing. Our findings reveal that YTHDC1 is overexpressed in CRPC and modulating its expression directly affects AR-V7 levels, rendering the cells sensitive to enzalutamide treatment. Mechanistically, we demonstrate that YTHDC1 binds to the AR-V7 pre-mRNA and facilitates the recruitment of phosphorylated SRSF1, a splice factor that promotes AR-V7 splicing. Additionally, we also demonstrate that it modulates the levels of CLK1, a known SRSF1 kinase supporting its role in regulating AR-V7 splicing. Furthermore, our experiments also reveal that YTHDC1 regulates the expression of other oncogenic transcripts, including Bcl-2, Cyclin D1, Nova1, and VEGF-A, highlighting its broader role in cancer progression. Overall, our study supports that targeting YTHDC1 could be a novel therapeutic approach to overcome AR-V7-mediated treatment resistance in CRPC patients.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"5157-5172"},"PeriodicalIF":3.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144128348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Risk factors for cognitive decline in type 2 diabetes mellitus adults: a systematic review and meta-analysis.","authors":"Shengcheng Mao, Yingmin Wang","doi":"10.1007/s11010-025-05306-y","DOIUrl":"10.1007/s11010-025-05306-y","url":null,"abstract":"<p><p>Cognitive decline (CD) is a common disorder in patients with type 2 diabetes mellitus (T2DM), which is affected by various factors. The present study aimed to investigate the factors affecting its occurrence CD in patients T2DM. The PubMed, Web of Science, Scopus, and Embase databases were searched for pertinent research on the risk factors for the beginning of CD. The remaining studies were assessed using predetermined inclusion and exclusion criteria after duplicate studies were eliminated. The Comprehensive Meta-Analysis software (version 2) was used to analyze the data. The Egger test and Begg and Mazumdar test was used to examine publication bias, while the I-square statistic was used to evaluate study heterogeneity. 95% confidence limits and odds ratios were used in the analysis. 40 studies were authorized for assessment and statistical analysis using the systematic review procedure. These studies' findings indicate that, using both crude and adjusted analyses, the odds ratio for the occurrence of CD in people with diabetes is higher for factors like low educational attainment, men, abnormal Hemoglobin A1c (HbA1C) levels, physical inactivity, depression, and stroke. Factors like low education, abnormal HbA1C levels, depression, and stroke as well increase the risk of developing CD in diabetic patients. These cases in diabetic patients require special attention.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"4961-4972"},"PeriodicalIF":3.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144120276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yi Zhang, Cuicui Cao, Chang Sun, Jie Yan, Yuelan Wang, Changping Gu
{"title":"The SIRT1/GPS2/AIP1 axis regulates pulmonary vascular permeability in ventilator-induced lung injury.","authors":"Yi Zhang, Cuicui Cao, Chang Sun, Jie Yan, Yuelan Wang, Changping Gu","doi":"10.1007/s11010-025-05313-z","DOIUrl":"10.1007/s11010-025-05313-z","url":null,"abstract":"<p><p>Mechanical ventilation (MV) is essential for patients who require life support, but undue mechanical stress leads to airway and alveolar injury, also known as ventilator-induced lung injury (VILI). MV induces changes in pulmonary endothelial barrier integrity by affecting cell junction proteins. The mechanisms of disruption of endothelial barrier integrity during VILI are still unclear. This study aimed to investigate the roles and mechanisms by which ASK1-interacting protein-1 (AIP1), G-protein pathway suppressor 2 (GPS2), and sirtuin 1 (SIRT1) affect VILI. Human lung microvascular endothelial cells (HLMVECs) were transfected with AIP1 small interfering RNA (siRNA), GPS2 siRNA, GPS2 cDNA, and SIRT1 siRNA and subjected to 20% cyclic stretch (CS). C57BL/6N mice were pretreated with the SIRT1 siRNA before MV. We found that CS of 20% activated oxidative stress, increased the reactive oxygen species (ROS) production, and disrupted the pulmonary endothelial cell barrier integrity. AIP1 depletion increased the ROS production and aggravated the disruption of endothelial barrier integrity. Loss of GPS2 decreased the level of AIP1, leading to low expression levels of cell junction proteins. These effects were alleviated by GPS2 overexpression. SIRT1 depletion induced a decrease in GPS2 and AIP1, and increased the ROS production, resulting in decreased expression levels of cell junction proteins. Furthermore, VILI was exacerbated by increased cytokine production (IL-6 and IL-1β), pulmonary oedema, and an elevated wet/dry weight ratio in SIRT1-depleted mice under MV. These results suggest that cyclic mechanical stretching activated oxidative stress and disrupted the expression of cell junction proteins. The SIRT1/GPS2/AIP1 axis influences the production of ROS to regulate the pulmonary endothelial cell barrier integrity during VILI.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"5091-5103"},"PeriodicalIF":3.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Aberrant formation of the neutrophil extracellular trap and the expression of the PLEKHA1 in systemic lupus erythematosus and ulcerative colitis.","authors":"Jieyu Zhou, Yilin Guo, Ziying Tian, Zihan Lv, Su Jiang, Wenling Zhang","doi":"10.1007/s11010-025-05300-4","DOIUrl":"10.1007/s11010-025-05300-4","url":null,"abstract":"<p><p>Systemic lupus erythematosus (SLE) and ulcerative colitis (UC) are both chronic autoimmune diseases with unclear shared mechanisms, largely due to limited mechanistic studies and clinical research cohorts. Transcriptome datasets from the Gene Expression Omnibus (GEO) database were analyzed for SLE and UC, identifying differentially expressed genes (DEGs). Weighted gene co-expression network analysis (WGCNA) identified significant module genes, including PLEKHA1. The diagnostic potential of PLEKHA1 was confirmed using machine-learning algorithms and real-time fluorescence quantitative PCR (RT-PCR) in clinical samples. Additionally, the study explored the link between PLEKHA1 and neutrophil extracellular trap (NET) formation. Our analyses identified transcriptional signatures associated with neutrophil degranulation and NET formation pathways in the peripheral blood of both SLE and UC, a perspective not previously explored. PLEKHA1 was identified as a promising biomarker that may impact NET formation. Pathway enrichment analyses indicated that PLEKHA1 plays a regulatory role in NET formation in both diseases. This study provides novel transcriptional evidence by proposing neutrophil degranulation and NET formation as common pathways in SLE and UC, with PLEKHA1 acting as a shared diagnostic gene. PLEKHA1 may regulate neutrophil activation and immune response, influencing NET formation and neutrophil degranulation in SLE patients' peripheral blood.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"5041-5057"},"PeriodicalIF":3.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yogendra Singh Rajpurohit, Mitu Lal, Dhirendra Kumar Sharma, Ishu Soni
{"title":"Human TLS DNA polymerase: saviors or threats under replication stress?","authors":"Yogendra Singh Rajpurohit, Mitu Lal, Dhirendra Kumar Sharma, Ishu Soni","doi":"10.1007/s11010-025-05291-2","DOIUrl":"10.1007/s11010-025-05291-2","url":null,"abstract":"<p><p>The maintenance of genomic stability is crucial for life, threatened by DNA damage from both endogenous and exogenous sources. Cells employ DNA damage response through various repair mechanisms and DNA damage tolerance via translesion synthesis (TLS), to bypass DNA lesions and prevent replication fork collapse. This review explores the roles of human TLS polymerases in navigating replication stress, a critical process that can lead to genomic instability and cancer. It discusses TLS polymerase's dual role in genome preservation under certain physiological conditions while may also contribute to adaptive mutagenesis, highlighting their significance in DNA damage tolerance, somatic hypermutations, and cancer therapeutics. Understanding these mechanisms offers insights for developing targeted cancer therapies.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"4991-5008"},"PeriodicalIF":3.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12476452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144128343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Giovanna Sgrignani, Marta Iozzo, Lara Di Leonardo, Elisa Pardella, Erica Pranzini, Giulia Gangarossa, Giuseppina Comito, Luigi Ippolito, Elisa Giannoni, Paola Chiarugi
{"title":"GPR55 senses lactate to sustain motility in prostate cancer cells.","authors":"Giovanna Sgrignani, Marta Iozzo, Lara Di Leonardo, Elisa Pardella, Erica Pranzini, Giulia Gangarossa, Giuseppina Comito, Luigi Ippolito, Elisa Giannoni, Paola Chiarugi","doi":"10.1007/s11010-025-05312-0","DOIUrl":"10.1007/s11010-025-05312-0","url":null,"abstract":"<p><p>The enrichment of specific metabolites within the tumor microenvironment is emerging as a driver of tumor progression. Specifically, in prostate cancer (PCa), increased abundance of lactate is associated with primary-to-metastasis tumor spreading by supporting cancer cell invasiveness. Here, we highlight that the endocannabinoid receptor GPR55 is able to sense lactate and consequently trigger PCa cell amoeboid-like invasiveness, through the activation of the pro-migratory RhoA/MLC2 signaling pathway. These findings uncover a new role for GPR55 in sustaining lactate-driven PCa cell motility.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"5197-5204"},"PeriodicalIF":3.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12476429/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144160437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Anti-inflammatory effects and gut microbiota modulation of synbiotic mulberry in DSS-induced colitis rats.","authors":"Atcharaporn Ontawong, Arthid Thim-Uam, Sirinat Pengnet, Narongsuk Munkong, Pairote Wongputtisin, Kullanat Kuntakhut, Prathakphong Riyamongkhol, Dej Mann, Doungporn Amornlerdpison","doi":"10.1007/s11010-025-05309-9","DOIUrl":"10.1007/s11010-025-05309-9","url":null,"abstract":"<p><p>The global incident shows that the number of inflammatory bowel disease (IBD) cases increased by 88.30% in 2021 and significantly influenced patients' quality of life. Synbiotics are recommended as an alternative or supplement for IBD. We formulated synbiotic mulberry (SM) by mixing mulberry powder, probiotic biomass, and inulin. However, the anti-inflammatory effect of SM and gut microbiota modulation in dextran-sodium-sulfate (DSS)-induced colitis rats has not been thoroughly investigated. Thus, the anti-inflammatory activity of SM and gut microbiota composition was explored using DSS-induced acute colitis rats. Rats were divided into seven groups: control, control+SM1000, DSS, DSS+SM250, DSS+SM500, DSS+SM1000, and DSS+Sulfazalazine (SUL). All DSS induction rats received dissolving 4% (w/v) DSS in drinking water for 7 days, and their respective treatment was once daily via oral gavage. In addition, DSS-aggravated colitis rats received 0.4% (w/v) DSS in drinking water and their respective treatments once daily for the next 7 days. SM improved the disease activity index (DAI), body weight (BW), hepatosplenomegaly, colon length, and colon histomorphology, with outcomes similar to the results of SUL administration. Furthermore, SM decreased the levels of IL-6 production and suppressed iNOS and IL-10 mRNA expression in the colon. SM induced significant modulation in gut microbiota by significantly increasing the abundance of Allobaculu. SM also affects the amount of metabolic enzyme classes. In conclusion, we propose that SM may hold promise as a functional food therapeutic approach for the treatment of colitis; however, additional clinical trials are considered necessary to confirm these effects.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"5105-5121"},"PeriodicalIF":3.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144120274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}