Drug Development Research最新文献

{"title":"Repurposing Poloxamers as Antimicrobial Agents: A Comprehensive Review of Mechanisms and Applications","authors":"Sheila I. Peña Corona,&nbsp;Fabiola V. Borbolla-Jiménez,&nbsp;Lorena Duarte-Peña,&nbsp;Angélica Moreno,&nbsp;Luis E. Pérez-Caltzontzin,&nbsp;María Luisa Del Prado-Audelo,&nbsp;Alejandra Romero-Montero,&nbsp;Maykel González-Torres,&nbsp;Hernán Cortés,&nbsp;Hector Hernández-Parra,&nbsp;Javad Sharifi-Rad,&nbsp;Gerardo Leyva-Gómez","doi":"10.1002/ddr.70130","DOIUrl":"https://doi.org/10.1002/ddr.70130","url":null,"abstract":"<div>\u0000 \u0000 <p>In the last decades, the misuse and overuse of antimicrobial medications have precipitated the appearance of antimicrobial resistance, a phenomenon associated with around 4.95 million deaths per year worldwide. Control of this resistance represents the biggest challenge for antimicrobial therapies and novel drug formulations. Poloxamers are nonionic synthetic triblock copolymers used as excipients for formulating antibiotics, mainly as emulsifying agents, gelling agents, surfactants, and humectants. It has been discovered that poloxamers may have antimicrobial activity as microbicides or micro biostatics or can also potentiate other germicide drugs' efficacy. This review aims to examine the use of poloxamers and synthesize their potential mechanisms of action as antimicrobial drugs for treating microbial infections. This review's methodology included sourcing articles from PubMed, Google Scholar, and Scopus, using specific medical subject headings terms to warranty precision and pertinence. Poloxamer action mechanisms include quorum sensing inhibition, cellular membrane disruption, bacterial biofilm inhibition, and disruptions in bacteria cell walls. Results of Molecular docking demonstrated that poloxamers could interact directly with active sites of adhesion proteins and alter their functioning. Our experimental tests showed that poloxamers 188 and 407 possess the potential to be antimicrobial agents by effectively inhibiting <i>Staphylococcus aureus</i> and <i>Pseudomonas aeruginosa</i> growth. Despite the convincing evidence, further research is required to overcome challenges related to poloxamers' bioavailability and establish effective dosing regimens for different poloxamers to warrant their use and safety as antimicrobial drugs.</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 5","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144714689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Flavoxanthin Binds to AGR2 to Mediate Fatty Acid Oxidation and Reinforce Anoikis in Lung Adenocarcinoma","authors":"Meiling Sheng,&nbsp;Qunzhi Wang,&nbsp;Yabo Lou,&nbsp;Yuanchao Xiao,&nbsp;Xiaoming Wu","doi":"10.1002/ddr.70129","DOIUrl":"https://doi.org/10.1002/ddr.70129","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 <p>Traditional Chinese medicine (TCM) can not only alleviate symptoms in cancer patients and improve their life quality but also serve as an adjuvant therapy to reduce the toxic side effects of chemotherapy and radiotherapy, making it a hot topic in anti-tumor drug development in recent years. This project was designed to probe into the small molecular Chinese medicine components with targeted effects on lung adenocarcinoma (LUAD) and further reveal their mechanisms. Based on The Cancer Genome Atlas dataset analysis of anterior gradient-2 (AGR2) expression in LUAD, Autodock docking and scoring were employed to screen small molecular drugs that bound to AGR2. The gene set enrichment analysis was utilized to analyze enriched pathways of AGR2. By utilizing the cellular thermal shift assay, the binding relationship between Flavoxanthin and AGR2 was validated. The expression of AGR2, long-chain acyl-CoA synthetase (ACSL1), and carnitine palmitoyltransferase 1A was detected by reverse transcription-quantitative polymerase chain reaction. The cell counting kit-8 was leveraged to determine the half maximal inhibitory concentration (IC₅₀) and cell viability. Levels of fatty acid β-oxidation were measured, and BODIPY neutral lipid droplet staining was employed to evaluate fatty acid oxidation (FAO) intensity. The degree of anoikis was assessed by flow cytometry to detect apoptosis and western blot to detect anoikis-associated proteins. The immunohistochemistry was employed to measure the levels of Ki67 and Caspase-3. Tunel was applied to the detection of cell death. The result showed that flavoxanthin bound to highly-expressed AGR2 to reinforce anoikis in LUAD cells. Overexpression of AGR2 facilitated FAO inhibition of anoikis in LUAD. Flavoxanthin eliminated the promoting effect of AGR2 overexpression on FAO and restored the anoikis of LUAD cells. Animal experiments revealed that Flavoxanthin suppressed the malignant progression of LUAD through AGR2-mediated FAO. In conclusion, Flavoxanthin hinders FAO and boosts LUAD anoikis by targeting AGR2. These findings suggested that Flavoxanthin may be a novel option for intervention and treatment of LUAD, representing an instrumental advancement of small molecular components of TCM in modern oncology.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 5","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beta-Lapachone: Effects on Proliferation, Survival, Migration, Cell Cycle, and lncRNA Modulation in Bladder Cancer Cells With Distinct TP53 Profiles","authors":"Tatiane Roquete Amparo,&nbsp;Kamila de Fátima da Anunciação,&nbsp;Tamires Cunha Almeida,&nbsp;Glenda Nicioli da Silva,&nbsp;Geraldo Célio Brandão","doi":"10.1002/ddr.70128","DOIUrl":"https://doi.org/10.1002/ddr.70128","url":null,"abstract":"<div>\u0000 \u0000 <p>α-Lapachone (aLAP) and β-lapachone (bLAP) are noteworthy anticancer naphthoquinones. The chemoresistance observed in bladder cancer represents a global health concern, with relation to mutations in the <i>TP53</i> gene and alterations in the expression of long noncoding RNA (lncRNAs). This study evaluated the effects of aLAP and bLAP on bladder tumor cell lines with different <i>TP53</i> statuses: RT4 low-grade tumor with wild-type <i>TP53</i>), T24 and J82 (high-grade tumor with mutation in the <i>TP53</i> gene). Cytotoxicity was assessed using the MTT reduction method and cell migration by scratch assay, while clonogenic survival and cell cycle were evaluated through cell colony counting and flow cytometry, respectively. The expression of lncRNAs linked to bladder cancer and associated with tumor progression and prognosis (<i>JHDM1D-AS1</i>, <i>SBF2-AS1</i>, <i>CDT-2132N18.2</i>, and <i>RP11-363E7.4</i>) and the <i>JHDM1D</i> gene was evaluated through RT-qPCR. bLAP demonstrated greater cytotoxicity than aLAP. Its inhibitory effects on clonogenic survival, migration, and the cell cycle were observed in all cell lines and were related to the modulation of lncRNAs expression. A reduction in lncRNA <i>SBF2-AS1</i> and <i>JHDM1D</i> gene expression was observed in RT4 cells, accompanied by an increase in lncRNA <i>RP11-363E7.4</i>. Conversely, in the cells with mutated <i>TP53</i> (J82), a reduction in <i>JHDM1D-AS1</i> and <i>JHDM1D</i> was observed. The downregulation of <i>JHDM1D-AS1</i> and <i>SBF2-AS1</i>, along with the upregulation of <i>RP11-363E7.4</i>, may be associated with the observed inhibition of proliferation and cell migration following bLAP treatment. The antiproliferative effects of bLAP in bladder cancer cells are independent of <i>TP53</i> statuses, yet occur through a distinct action mechanism, with variations in lncRNAs expression.</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 5","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144647108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Vitro Leishmanicidal Efficacy of Synthesized Arylidene Analogues of Glitazone","authors":"Janine Aucamp,&nbsp;Helena D. Janse van Rensburg,&nbsp;Simon S. Mnyakeni-Moleele,&nbsp;Keisuke Suganuma,&nbsp;David D. N'Da","doi":"10.1002/ddr.70125","DOIUrl":"https://doi.org/10.1002/ddr.70125","url":null,"abstract":"<p>Diabetes is a fast-growing health issue in low- and middle-income countries, with ~80% of diabetics living in the tropics and sub-tropics. It is a deadly condition claiming the lives of millions of individuals annually, with no therapeutic treatment available to date. The management of diabetes is thus limited to symptomatic relief by glycemic control. Furthermore, the geographical overlap of diabetes and neglected tropical diseases (NTDs) is of concern, as diabetes is known to increase infection susceptibility and severity. In contrast, diabetes-infection comorbidity can negatively affect treatment responses. Leishmaniasis ranks among the top 10 NTDs. Its current therapeutic treatment relies on a handful of drugs that are marred with two main shortcomings: toxicity and reduced efficacy due to pathogenic resistance. Hence, there is a pressing need for new, effective antileishmanial therapeutics. There is evidence of rising cases of leishmaniasis-diabetes co-infection, which may require the use of dual-active therapeutics to curb them. In search of new effective antileishmanial agents with potential for dual use, we evaluated in vitro the antileishmanial and antidiabetic activities of a series of arylidenes derived from hydantoin, glitazone, and rhodanine scaffolds using phenotypic assays, some of which had previously been investigated for antidiabetic potential. Additionally, the antitrypanosomal potential of these compounds was also considered due to the taxonomic relation between <i>Leishmania</i> and <i>Trypanosoma</i> spp. and reported concerns of Chagas disease and human African trypanosomiasis-diabetes comorbidities. Three leishmanicidal early leads with submicromolar activity were uncovered, but no antitrypanosomal or dual leishmaniasis-diabetes active hits were identified.</p>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 5","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ddr.70125","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144615263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reduced Taurine Transporter Expression in Lymphoblastoid Cell Lines From Alzheimer's Disease Patients Compared With Age-Matched Controls: Therapeutic Implications?","authors":"Yuval Gavriel,&nbsp;Irena Voinsky,&nbsp;Hana Klin,&nbsp;Alessio Squassina,&nbsp;David Gurwitz","doi":"10.1002/ddr.70124","DOIUrl":"https://doi.org/10.1002/ddr.70124","url":null,"abstract":"<p>Taurine is an atypical amino acid that cannot form peptide bonds and thus does not take place in building proteins. Yet, taurine takes part in regulating many cell functions, including cell osmolarity and volume, mitochondrial function, membrane ion channels and neuronal activity, and cell survival. Taurine is synthesized by the liver, and available from consumption of meat and fish, but not plants. It has millimolar concentrations in the brain, skeletal muscle, blood, heart, retina, and other tissues. Taurine is transported from the liver (following synthesis) or the intestine (following consumption) to blood by the taurine transporter, encoded in humans by <i>SLC6A6</i>. A recent study reported that blood taurine declines dramatically in aged individuals. Several studies indicated that dietary taurine slows cognitive decline in Alzheimer's disease (AD) model mice. We therefore measured <i>SLC6A6</i> mRNA expression in human lymphoblastoid cell lines (LCLs) from AD patients and age-matched controls and observed 2.8-fold lower expression in AD LCLs (<i>p</i> = 0.0005). Additionally, glutathione peroxidase 1 (<i>GPX1</i>), a key free-radical scavenging selenoenzyme, had reduced mRNA expression in LCLs from AD patients compared with controls. Our observations suggest that reduced taurine transporter expression may contribute to AD pathogenesis and that dietary taurine might be beneficial for slowing disease progression in early-stage AD. Clinical trials with dietary taurine supplementation of individuals with mild cognitive impairment (MCI) or early-stage AD are required to assess its tentative therapeutic potential.</p>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 5","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ddr.70124","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144581896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRPC1 and TRPC5 in Colorectal Cancer: Mechanisms, Prognostic Markers, and Therapeutic Targets","authors":"Manal A. Abbas,&nbsp;Aya Y. Al-Kabariti,&nbsp;Randa El-Rayyes,&nbsp;Razan Obeidat,&nbsp;Abd-Alrahman Al-Rayyes","doi":"10.1002/ddr.70123","DOIUrl":"https://doi.org/10.1002/ddr.70123","url":null,"abstract":"<div>\u0000 \u0000 <p>Colorectal cancer (CRC) is one of the most frequent and deadliest cancers worldwide, ranking third in prevalence and second in cancer-related deaths. Treating CRC remains a major challenge due to several factors: many cases are diagnosed at advanced stages, variable response to treatment due to genetic differences in patients, chemotherapy resistance, and the adverse effects of existing therapies. This highlights the urgent need for early diagnostic markers and effective treatments with fewer side effects. Recent research has identified transient receptor potential canonical (TRPC) channels as key regulators in the development and progression of cancer, although their specific role in CRC is not yet fully characterized. This review summarizes TRPCs pathophysiological functions, signaling pathways, interactions with other calcium channels, and their potential use as diagnostic and prognostic tools in clinical practice. Special emphasis is given to TRPC1 and TRPC5, as they represent the most extensively studied members of the TRPC family. This review also discusses potential therapeutic approaches targeting them, offering valuable insights for further advances in CRC research.</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 5","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144589624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AMPK/mTOR/ULK1 Pathway Participates in Autophagy Induction by Curcumin in Colorectal Adenoma Mouse Model","authors":"Yuge Wang,&nbsp;Moxixuan Liu,&nbsp;Xuemei Jia,&nbsp;Qian Yang,&nbsp;Yao Du","doi":"10.1002/ddr.70115","DOIUrl":"https://doi.org/10.1002/ddr.70115","url":null,"abstract":"<div>\u0000 \u0000 <p>Colorectal adenoma (CRA) represents a pathological condition characterized by the aberrant development of intestinal epithelial cells and alterations in cellular differentiation within the colorectal mucosal epithelium, posing an increased risk for malignant transformation if not adequately addressed. Curcumin has been shown to exhibit a range of therapeutic effects across various diseases, which motivated this investigation utilizing C57BL/6 mice as a model system. Methodologies including hematoxylin-eosin staining (HE), western blot analysis, RT-PCR, immunofluorescence, and electron microscopy were employed to evaluate proteins associated with the <i>AMPK/mTOR/ULK1</i> signaling pathway. The study specifically examined variations in key autophagy-related proteins such as <i>Beclin-1, LC3, P62</i>, alongside intestinal junction proteins <i>Occludin, ZO-1, and Claudin-1</i>. This study seeks to elucidate whether curcumin can influence autophagy-related mechanisms in intestinal mucosal epithelial cells affected by colorectal adenoma to achieve potential therapeutic outcomes.</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 5","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144589625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis and Biological Activity of Benzoselenazole and Benzo[b]Selenophene Analogues: A Review","authors":"Jia Li,&nbsp;Jingmin Chen,&nbsp;Jiayao Liu,&nbsp;Xudong Zhou,&nbsp;Yangyang Li,&nbsp;Wei Wang,&nbsp;Wenbing Sheng","doi":"10.1002/ddr.70127","DOIUrl":"https://doi.org/10.1002/ddr.70127","url":null,"abstract":"<div>\u0000 \u0000 <p>Selenium, an essential micronutrient in the human body, not only exhibits potent antioxidant properties but also plays a critical role in regulating thyroid hormone metabolism, maintaining normal immune function, and inhibiting tumour progression. Among selenium-containing compounds, ebselen is the most extensively studied drug candidate. Research has shown that various derivatives obtained through structural modifications of Ebselen exhibits significant biological activities; however, these compounds have yet to progress to clinical trials. Consequently, selenium-containing heterocyclic compounds represent a promising avenue for drug discovery and development. This review summarizes three synthetic approaches for constructing selenium-containing heterocyclic compounds and emphasizes their notable biological activities and potential applications in pharmaceuticals.</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 5","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144573762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phoenixin-14 Alleviates Premature Ovarian Failure by Inhibiting Ferroptosis Through SLC7A11/GPX4","authors":"Rong Wu,&nbsp;Ting Wang,&nbsp;Xiaofeng Xu,&nbsp;Ying Wang,&nbsp;Jingjing Hu,&nbsp;Wenjuan Yang,&nbsp;Xiao Wu,&nbsp;Zhaolian Wei","doi":"10.1002/ddr.70110","DOIUrl":"https://doi.org/10.1002/ddr.70110","url":null,"abstract":"<div>\u0000 \u0000 <p>Premature ovarian failure (POF) is a complex condition marked by early ovarian decline, reduced follicular reserve, and compromised oocyte quality. Oxidative stress (OS) and ferroptosis are critical drivers of POF progression. This study investigates the therapeutic potential of Phoenixin-14 (PNX-14) in alleviating POF in rats by modulating granulosa cell (GC) ferroptosis through the ATF4/SLC7A11/GPX4 signaling pathway. Cisplatin-induced POF rat models were used to evaluate PNX-14's effects on ovarian function, oxidative stress (MDA/SOD), and ferroptosis. Serum PNX-14 levels, GPR173 expression, body/ovarian weights, follicle development, and oxidative markers were analyzed. In cisplatin-induced POF rat models, serum PNX-14 levels and GPR173 expression were significantly downregulated, suggesting potential impairment of the PNX-14/GPR173 axis. PNX-14 administration improved body and ovarian weights, restored ovarian tissue structure, and reduced oxidative damage, as evidenced by reduced MDA levels and enhanced SOD activity. At the molecular level, PNX-14 suppressed ferroptosis in GCs by enhancing ATF4 expression, which in turn upregulated SLC7A11 and GPX4, critical components of cellular antioxidant defense. Caspase-3 assays suggested minimal apoptosis in cisplatin-treated cells. PNX-14 showed similar effectiveness to Fer-1 in reducing cisplatin-induced ferroptosis, evidenced by restored viability, lower Fe²⁺, and reduced MDA, without added benefit when combined. Silencing ATF4 reversed the beneficial effects of PNX-14 on GC viability and ferroptosis, confirming the pivotal role of ATF4 in mediating the protective effects of PNX-14. These results suggest that PNX-14 alleviates POF by inhibiting GC ferroptosis through the ATF4/SLC7A11/GPX4 axis, providing a potential therapeutic strategy for POF management.</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 5","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144367361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Management of Alzheimer's Disease With Nanotechnological Interventions and Novel Therapeutics","authors":"Mohd Shahrukh,&nbsp;Shadaan Ahmad,&nbsp;Mohammed Zaafar,&nbsp;Nazeer Hasan,&nbsp;Farhan Jalees Ahmad","doi":"10.1002/ddr.70120","DOIUrl":"https://doi.org/10.1002/ddr.70120","url":null,"abstract":"<div>\u0000 \u0000 <p>Alzheimer's disease (AD) is a progressive neurodegenerative condition marked by cognitive deterioration, β-amyloid plaque buildup, intracellular tangles, and significant neuronal loss. The increasing prevalence of AD, along with its substantial economic burden, underscores the urgent need for effective therapeutic strategies in the near future. The challenge is early diagnosis and management, hindered by the lack of reliable biomarkers. Currently, there is no definitive cure for AD. Attaining improved therapeutic outcomes necessitates delivering optimal drug concentrations to the central nervous system (CNS) by effectively penetrating the blood–brain barrier (BBB). Recently, nanotechnology has emerged as a promising approach to address this challenge, enhancing brain-targeted drug delivery while highlighting recent advancements and future potential. Additionally, novel targeted therapies such as genetic therapeutics, stem cell therapy, and immunotherapy approaches overcome AD-based challenges, enhance treatment efficacy, and improve patient compliance. This review highlights recent advancements in the treatment of AD, focusing on nanotechnology-based drug delivery systems, and also explores genetic therapeutics, stem cell therapy, and immunotherapy approaches. Overall, the review provides a comprehensive overview of these therapeutic approaches, shedding light on the evolving landscape of AD treatment and the challenges that lie ahead.</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 5","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144367364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}