Molecular and Cellular Biochemistry最新文献

{"title":"Ferritinophagy in cardiovascular diseases: mechanisms and potential therapy.","authors":"Shuyue Wang, Zengzhao Yu, Lin Ye, Dandan Xiao, Puhan Wang, Yu Wang, Jianxun Wang","doi":"10.1007/s11010-025-05301-3","DOIUrl":"https://doi.org/10.1007/s11010-025-05301-3","url":null,"abstract":"<p><p>The process of ferritinophagy, which involves the selective autophagic breakdown of ferritin triggered by nuclear receptor coactivator 4 (NCOA4), has been shown to regulate ferroptosis. Recent studies have confirmed that ferritinophagy plays a key role in the formation and progression of cardiovascular diseases. The mechanism of ferritinophagy involves the phagocytosis of ferritin by NCOA4, which binds ferritin and delivers it to the autophagosome. There, it fuses with lysosomes to degrade ferritin and release iron. This process is not only involved in iron-dependent responses, but also in the progression of a variety of human diseases, including metabolism-related diseases, neurodegenerative diseases, cardiovascular diseases, and infectious diseases. In cardiovascular diseases, ferritinophagy plays a central role in inducing ferroptosis, a mode of programmed cell death caused by lipid peroxidation. This process is regulated by intracellular iron homeostasis and reactive oxygen species production. It has been demonstrated that ferritinophagy promotes ferroptosis by increasing intracellular iron content. Furthermore, the influence of ferritinophagy in cardiovascular diseases has been further demonstrated. For instance, ischemia-reperfusion injury, atherosclerosis, myocardial disease and heart failure are all associated with ferritin levels. The early detection of ferritin levels, maintenance of iron homeostasis, prevention of iron overload and exploration of the interrelationship between ferritinophagy and cardiac diseases can provide new ideas for the prevention and treatment of cardiovascular diseases. Therapeutic options for ferritinophagy are also being explored. For instance, the inhibition of O-GlcNAcylation modification has been shown to promote ferritinophagy, which releases iron stored in ferritin and further regulates ferroptosis. Ferritinophagy has been demonstrated to play an important role in the formation and progression of cardiovascular diseases, influencing disease development by regulating iron homeostasis and ferroptosis. Future studies may further reveal the specific mechanisms and develop new therapeutic strategies.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333517","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":"Gut microbiota diversity and metabolomics analysis of curcumin's alleviation of abdominal aortic aneurysm progression.","authors":"Shuai Cheng, Xinyu Hao, Lei Wang, Bo Jiang, Shijie Xin","doi":"10.1007/s11010-025-05314-y","DOIUrl":"https://doi.org/10.1007/s11010-025-05314-y","url":null,"abstract":"<p><p>Abdominal aortic aneurysm (AAA) is a high-risk vascular condition with a significant need for effective treatments to slow its progression, particularly for small-diameter AAAs. While previous studies have demonstrated curcumin's beneficial effects in AAA mouse models, the role of gut microbiota homeostasis and metabolic changes in this context remains poorly understood. We developed a recently established AAA mouse model and assessed alterations in the gut microbiota. We also examined the effect of curcumin on AAA progression. Fecal samples from different groups of mice were collected and analyzed using 16 s rRNA sequencing to explore the role of gut microbiota in curcumin's therapeutic actions, while serum samples were analyzed by LC-MS/MS to investigate metabolic changes associated with curcumin's therapeutic effects. In a mouse AAA model induced by elastase periadventitial incubation combined with β-aminopropionitrile (BAPN), we observed reduced gut microbiota diversity and a decrease in several probiotic genera. Curcumin treatment inhibited AAA progression, reduced pathological aortic changes and downregulated the expression of pro-inflammatory cytokines. Additionally, curcumin prevented the phenotypic shift of vascular smooth muscle cells from a contractile to a synthetic state. Notably, curcumin improved gut microbiota diversity, increased probiotic genera abundance. Finally, curcumin modulated the serum metabolic profile, alleviating AAA-related metabolic changes. Curcumin enhances gut microbiota homeostasis, modulates metabolic changes, and inhibits AAA progression, offering new insights into its therapeutic potential for AAA management.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310206","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":"Piezo1: the Potential Novel Target for Radiation-induced Liver Fibrosis by Regulating FAP + fibroblasts.","authors":"Wentong Liu, Haochen Zou, Jiaying Wei, Lihua Dong, Wei Hou","doi":"10.1007/s11010-025-05327-7","DOIUrl":"https://doi.org/10.1007/s11010-025-05327-7","url":null,"abstract":"<p><p>Radiation-induced liver fibrosis is a serious complication of radiotherapy in patients with liver cancer and is characterized by excessive deposition of the extracellular matrix (ECM). The activation of cancer-associated fibroblasts (CAFs) is central to this event. Piezo1 is a mechanoreceptor that is highly expressed in liver tissue and is closely related to the fibrotic process. CAFs are highly heterogeneous, and different cell populations perform different functions. Recent studies have shown that fap, an important surface marker of the CAF membrane, presumably plays a \"hub\" role upstream of α-smooth muscle actin (α-SMA). This article reviews the unique microenvironment of liver cancer and liver fibrosis and the role of piezo1 and CAFs in liver fibrosis. Building upon the foundational evidence, we formulate a hypothesis that radiation-induced ECM remodeling activates Piezo1-mediated mechanotransduction, driving HIF-1α/TGF-β pathways to stimulate CAF activation (manifested by FAP upregulation), which may synergistically aggravate liver fibrosis and hepatocarcinogenesis.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317478","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":"The role of lncRNA-ZFAS1 in liver fibrosis: insights into the miR-1953/TAZ axis.","authors":"Binbo Fang, Weizhi Zhang, Mengyuan Li, Jianjian Zheng, Hui Jin","doi":"10.1007/s11010-025-05335-7","DOIUrl":"https://doi.org/10.1007/s11010-025-05335-7","url":null,"abstract":"<p><p>Long non-coding RNA-Zinc finger antisense 1 (lncRNA-ZFAS1) is involved in the progression of several cancer types, yet its function in liver fibrosis remains unclear. The purpose of this study was to examine ZFAS1 expression in liver fibrosis and explore its possible molecular mechanism. ZFAS1 expression was measured in a liver fibrosis model and in activated hepatic stellate cells (HSCs). The impact of ZFAS1 silencing on HSC growth, collagen production, and epithelial-mesenchymal transition (EMT) was assessed. The connection between ZFAS1 and miR-1953 was investigated using bioinformatics analysis and luciferase reporter gene experiments. Moreover, in vivo studies were performed to confirm the effect of ZFAS1 knockdown on liver fibrosis progression. ZFAS1 was significantly upregulated in the liver fibrosis model and activated HSCs. Silencing ZFAS1 helped to inhibit the growth and activation of HSCs, along with reduced levels of type I collagen and α-SMA. In vivo experiments confirmed that ZFAS1 knockdown alleviated the progression of fibrosis and collagen deposition. Mechanistic studies revealed that ZFAS1 promoted HSC EMT through the regulation of the miR-1953/TAZ axis, thereby exerting a pro-fibrotic effect. By influencing the miR-1953/TAZ signaling pathway, ZFAS1 significantly contributes to the activation and EMT of HSCs in liver fibrosis development. These findings highlight ZFAS1 as a potential therapeutic target for treating liver fibrosis, offering new avenues for clinical intervention.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317479","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":"Updated insights on ASK1 signaling: mechanisms, regulation, and therapeutic potential in diseases.","authors":"Divyanshi Thakur, Aniket Nandi, Yash Kumar Gaur, Karthikeyan Chandrabose, Digambar Kumar Waiker, Ghanshyam Das Gupta, Kalicharan Sharma","doi":"10.1007/s11010-025-05330-y","DOIUrl":"https://doi.org/10.1007/s11010-025-05330-y","url":null,"abstract":"<p><p>Apoptosis signal-regulating kinase 1 (ASK1) is a serine-threonine kinase, that is a member of the mitogen-activated protein kinase kinase (MAP3K) family, which is expressed or incorporated in nucleated cells which leads to the activation of multiple mitogen-activated protein kinases (MAPK) to regulate cell stress, tumour necrosis factor-α (TNF-α) ligand, lipopolysaccharides and apoptosis. ASK1 gets activated by the ROS, oxidative stress, endoplasmic stress (ER) and various inflammatory cytokines. Dysregulation of ASK1 can lead to various diseases like neurodegenerative disease, cardiovascular disease, cancer, and various other metabolic diseases such as diabetes. This review summarizes ASK1's structure, its family, regulation, and its dual role in disease, highlighting its therapeutic potential for oxidative stress and inflammation-driven conditions while emphasizing the need for further clinical research. Inhibition of ASK1 demonstrates promising potential in treating fibrosis and various other diseases. We also discuss the dual role of ASK1 in both cancer initiation and suppression. Additionally, we explore ASK1 as a therapeutic target in diseases driven by oxidative stress and inflammation, emphasizing the need for further research to support its clinical translation.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144294109","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":"Gut-brain-immune axis implications for mental health and disease.","authors":"Hadi Nasiri, Zahra Valedkarimi, Morteza Akbari","doi":"10.1007/s11010-025-05325-9","DOIUrl":"https://doi.org/10.1007/s11010-025-05325-9","url":null,"abstract":"<p><p>Significantly affecting mental health, the gut-brain-immune axis shows a complicated interaction between the gastrointestinal tract, immune system, and central nervous system. Maintaining immunological homeostasis and brain function depends on gut bacteria, which are crucial due to their varied microbial populations. Along this axis, communication takes place via immunological responses, microbial metabolites, and brain pathways. Mental health issues like stress, sadness, autism spectrum disorders (ASD), and schizophrenia are linked to dysbiosis and inflammation. Restoring microbial balance and enhancing mental health outcomes show promise from therapeutic approaches, including probiotics, prebiotics, dietary changes, and pharmaceutical and non-pharmacological therapies. Future studies should concentrate on clarifying the gut-brain-immune axis mechanics, creating individualized treatments, and applying results into clinical use. By tackling their underlying causes and encouraging general well-being, this combined approach presents fresh paths for treating mental health problems.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275393","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":"TAP1 promotes immune escape by activating JNK/STAT1/PD-L1 signaling in EBV-associated gastric cancer.","authors":"Wenqing Shan, Guoqingyuan Li, Hailing Zhang, Ranran Zhang, Jialong Liu, Liping Gao, Yizhang Li, Lilan Fan, Chaoran Yang, Jing Liu","doi":"10.1007/s11010-025-05319-7","DOIUrl":"https://doi.org/10.1007/s11010-025-05319-7","url":null,"abstract":"<p><p>Epstein-Barr virus (EBV) infection accounts for approximately 10% of gastric cancer (GC) cases and is strongly linked to immune evasion, although the precise mechanisms remain unclear. Transporter associated with antigen processing 1 (TAP1), a member of ATP-binding cassette subfamily B, is overexpressed in EBV-associated gastric cancer (EBVaGC) and is implicated in tumor immune evasion. TAP1 expression levels in EBV-positive and EBV-negative gastric cancer samples were analyzed using TCGA and GEO datasets. Molecular biology techniques were used to investigate the regulatory pathways involved in TAP1. The role of TAP1 in modulating immunotherapy responses was validated using T-cell cytotoxicity assays and mouse models. TAP1 was significantly overexpressed in EBV-positive gastric cancer tissues and cell lines. Mechanistic studies revealed that EBV latent membrane protein 2A (LMP2A) activates the NF-κB P65 pathway, which directly binds to the TAP1 promoter and enhances transcription. Furthermore, TAP1 expression was positively correlated with PD-L1 levels. In immunocompetent mice, shTAP1 MFC cells exhibited significantly reduced growth relative to that in immunodeficient mice. TAP1 upregulates PD-L1 via the JNK/STAT1 pathway, thereby influencing tumor immunotherapy responses. Notably, TAP1 silencing combined with PD-1 monoclonal antibody treatment significantly inhibited gastric cancer cell proliferation. This study revealed a mechanism through which the EBV protein LMP2A drives TAP1 expression via NF-κB signaling. TAP1, in turn, regulates PD-L1 expression via the JNK/STAT1 pathway, contributing to immune evasion. These findings highlight TAP1 as a promising therapeutic target for improving the efficacy of immunotherapy in gastric cancer.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275394","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":"FOXM1 upregulation, promotes immune escape in gastric cancer through activation of Notch signaling pathway.","authors":"Shangkun Du, Ping Li, Yabin Liu, Bindan Cai, Gang Li, Wenbin Wang, Rui Yan, Xiangkui Zheng, Tianliang Bai","doi":"10.1007/s11010-025-05322-y","DOIUrl":"https://doi.org/10.1007/s11010-025-05322-y","url":null,"abstract":"<p><p>Forkhead box M1 (FOXM1) exhibits elevated level in various tumors and is linked with tumor immune escape. The role of FOXM1 in gastric cancer (GC) progression and immune escape remains poorly understood. FOXM1 and programmed death-ligand 1 (PD-L1) levels were determined through qRT-PCR and Western blot. Co-immunoprecipitation confirmed the interaction between FOXM1 and PD-L1. The malignant biological properties of GC cells were assessed by MTT, EdU staining, scratch-wound assay, transwell and flow cytometry. CD8 + T cells were separated and co-cultured with GC cells, and the proliferation and apoptosis of CD8 + T cells were detected through CFSE staining, flow cytometry and LDH kit. CD8 + T cytokine contents were measured using ELISA kits. Western blot detected CD8 + T cell activation markers and Notch signaling pathway-related proteins levels. A nude mouse subcutaneous graft tumor model was constructed, Ki-67 positivity and CD8 + T cell infiltration were detected by immunohistochemistry and flow cytometry. FOXM1 and PD-L1 were highly expressed in GC. Overexpression of FOXM1 increased migrating and infiltrating cell counts and GC cell viability, and declined the killing impact of CD8 + T cells. After knockdown of FOXM1, all of the above indicators were significantly reversed. After co-cultured with GC cells overexpressing FOXM1, CD8 + T cells exhibited a declined in CFSE positivity percentage, cytotoxicity, cytokines and activation markers levels, and an increase in apoptosis. FOXM1 up-regulated PD-L1 expression by activating the Notch signaling pathway, and both silencing PD-L1 and Notch inhibitor attenuated the impact of overexpression of FOXM1. Knockdown of FOXM1 reduced Ki67 positivity in GC tumors and promoted CD8 + T cell infiltration. FOXM1 up-regulates PD-L1 level by activating Notch signaling pathway, thus hinders CD8 + T cell activation and promotes immune escape in GC cells. This study provides a theoretical basis for the development of GC-targeted therapeutic targets as well as immunotherapy, which is beneficial to the clinical diagnosis and treatment of GC.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266726","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":"Bone marrow mesenchymal stem cells promote the recovery of stroke in rats with type 2 diabetes mellitus by inhibiting the activation of TLR4/NF-κB signaling pathway.","authors":"Fan Peng, Yanping Long, Taolin Zheng, Minghui Leng, Hui Deng","doi":"10.1007/s11010-025-05332-w","DOIUrl":"https://doi.org/10.1007/s11010-025-05332-w","url":null,"abstract":"<p><p>Ischemic stroke is a major complication of type 2 diabetes mellitus (T2DM), significantly contributing to increased mortality in T2DM patients. Bone marrow mesenchymal stem cells (BMSCs), known for their multidirectional differentiation potential, have shown therapeutic potential in treating ischemic stroke associated with T2DM; however, the underlying mechanisms remain unclear. This study aimed to investigate the therapeutic effects and mechanisms of BMSCs in T2DM-related ischemic stroke. A T2DM rat model was established and subjected to transient middle cerebral artery occlusion (MCAO) to induce ischemic stroke. BMSCs were administered to evaluate their effects on body weight, blood glucose levels, modified neurological severity score (mNSS), infarct volume, and blood-brain barrier (BBB) integrity in T2DM-MCAO rats. RNA sequencing was performed on brain tissues from T2DM-MCAO rats before and after BMSCs treatment to identify differentially expressed genes (DEGs). Functional enrichment analysis, including Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, quantitative real-time PCR, and western blot, were conducted to explore the underlying mechanisms. The results demonstrated that T2DM-MCAO rats exhibited increased body weight, elevated blood glucose levels, higher mNSS scores, larger brain infarct volumes, and BBB disruption, all of which were partially ameliorated by BMSCs treatment. Furthermore, BMSCs downregulated the expression of TLR4 and reduced the protein levels of p65 and phosphorylated p65 (p-p65), which were upregulated in T2DM-MCAO rats. Overexpression of TLR4 partially reversed the beneficial effects of BMSCs on functional outcomes, infarct volume, and BBB integrity. In conclusion, this study demonstrates that BMSCs alleviate T2DM-related ischemic stroke by suppressing TLR4 expression and inhibiting the TLR4/NF-κB signaling pathway, suggesting a potential therapeutic target for T2DM-associated ischemic stroke.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275392","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":"The role of L-DOPA in neurological and neurodegenerative complications: a review.","authors":"Sudheendra Rao Kulkarni, Bothe Thokchom, Megha B Abbigeri, Santosh Mallikarjun Bhavi, Sapam Riches Singh, Nitish Metri, Ramesh Babu Yarajarla","doi":"10.1007/s11010-025-05324-w","DOIUrl":"https://doi.org/10.1007/s11010-025-05324-w","url":null,"abstract":"<p><p>L-DOPA remains a cornerstone treatment for Parkinson's disease and is increasingly recognized for its role in various neurological and neurodegenerative disorders. As a direct precursor to dopamine, L-DOPA is synthesized from L-tyrosine through the action of tyrosine hydroxylase and is subsequently converted into dopamine via aromatic L-amino acid decarboxylase. Its ability to cross the blood-brain barrier (BBB) makes it a crucial therapeutic agent for restoring dopaminergic neurotransmission, thereby influencing motor function, cognition, and neuroprotection. Beyond Parkinson's, L-DOPA's therapeutic potential extends to neurodegenerative conditions such as Alzheimer's disease, Huntington's disease, multiple sclerosis, Lewy body dementia, and amyotrophic lateral sclerosis, where dopamine modulation plays a critical role. Furthermore, L-DOPA has demonstrated efficacy in neurological disorders including epilepsy, peripheral neuropathy, cerebrovascular diseases, and traumatic brain injury, suggesting broader neurobiological applications. However, long-term use is associated with challenges such as motor fluctuations, dyskinesias, and loss of therapeutic efficacy due to progressive neurodegeneration and alterations in dopaminergic pathways. Recent advancements in drug delivery systems, combination therapies, and nanotechnology, including plant-derived carbon dots, offer promising strategies to enhance L-DOPA's effectiveness while mitigating its limitations. This comprehensive review explores L-DOPA's synthesis, pharmacokinetics, mechanism of action, and its evolving role in neurological diseases, while highlighting ongoing challenges and future directions for optimizing its clinical application.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248705","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}