Current Alzheimer research最新文献

{"title":"Mapping the Connection Between Circadian Rhythms, Metabolism, and Neurodegeneration: Exploring Therapeutic Strategies.","authors":"Rakesh Bhaskar, Kannan Badri Narayanan, Krishna Kumar Singh, Sung Soo Han","doi":"10.2174/0115672050381989250626071304","DOIUrl":"https://doi.org/10.2174/0115672050381989250626071304","url":null,"abstract":"<p><p>Circadian rhythms are crucial for essential physiological functions such as metabolism, sleep-wake cycles, hormone balance, and cognitive abilities, which are regulated by the central Suprachiasmatic Nucleus (SCN) and peripheral clocks. Disruptions to circadian rhythms, which may be caused by aging, lifestyle factors, and environmental influences, are linked to metabolic disorders and Neurodegenerative Diseases (NDs). This review examines the reciprocal relationship between circadian control and metabolism, highlighting the molecular processes that maintain circadian rhythms and how these processes change with age. Aging diminishes SCN efficiency and disrupts peripheral clock alignment, leading to impaired physiological functions, increased oxidative stress, and neuroinflammation, all of which contribute to the progression of NDs such as Alzheimer's (AD), Parkinson's disease (PD), Huntington's disease (HD), etc. Emerging therapeutic strategies aim to restore circadian function through interventions, including bright light therapy, melatonin supplementation, and pharmacological agents targeting clock gene regulators and neuropeptides. Furthermore, lifestyle modifications, such as Structured Physical Activity (SPA) and Time-Restricted Feeding (TRF), can enhance circadian health by synchronizing metabolic and hormonal rhythms. Future directions include chrono-pharmacology, gene editing, and Artificial Intelligence (AI)-driven personalized medicine, all of which emphasize the development of tailored circadian therapies. Advancing circadian research holds the potential to facilitate better health outcomes and improve quality of life, while also addressing the growing concerns of the aging population and NDs.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144661507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effective Analysis of Alzheimer's Disease and Mechanisms of Methyl-4- Hydroxybenzoate using Network Toxicology, Molecular Docking, and Machine Learning Strategies.","authors":"Jianren Wen, Jingxuan Hu, Xue Yang, Feifei Luo, Guohui Zou","doi":"10.2174/0115672050399031250623062112","DOIUrl":"https://doi.org/10.2174/0115672050399031250623062112","url":null,"abstract":"<p><strong>Introduction: </strong>Nowadays, the large increase in environmental pollutants has led to the occurrence and development of an increasing number of diseases. Studies have shown that exposure to environmental pollutants, such as methyl-4-hydroxybenzoate (MEP) may lead to Alzheimer's disease (AD). Therefore, the purpose of this study was to elucidate the complex effects and potential molecular mechanisms of environmental pollutants MEP on AD.</p><p><strong>Methods: </strong>Through exhaustive exploration of databases, such as ChEMBL, STITCH, SwissTarget- Prediction, and Gene Expression Omnibus DataSets (GEO DataSets), we have identified a comprehensive list of 46 potential targets closely related to MEP and AD. After rigorous screening using the STRING platform and Cytoscape software, we narrowed the list to nine candidate targets and ultimately identified six hub targets using three proven machine learning methods (LASSO, RF, and SVM): CREBBP, BCL6, CXCR4, GRIN1, GOT2, and ITGA5. The \"clusterProfiler\" R package was used to conduct GO and KEGG enrichment analysis. At the same time, we also constructed disease prediction models for core genes. At last, six hub targets were executed molecular docking.</p><p><strong>Results: </strong>We derived 46 key target genes related to MEP and AD and conducted gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. MEP might play a role in AD by affecting the pathways of neuroactive ligand-receptor interaction. Nine genes were screened as pivotal targets, followed by machine learning methods to identify six hub targets. Molecular docking analysis showed a good binding ability between MEP and CREBBP, BCL6, CXCR4, GRIN1, GOT2 and ITGA5. In addition, changes in the immune microenvironment revealed a significant impact of immune status on AD.</p><p><strong>Discussions: </strong>This study revealed that MEP may induce AD through multiple mechanisms, such as oxidative stress, neurotoxicity, and immune regulation, and identified six core targets (CREBBP, BCL6, etc.) and found that they are related to changes in the immune microenvironment, such as T cells and B cells, providing new molecular targets for AD intervention.</p><p><strong>Conclusion: </strong>Overall, CREBBP, BCL6, CXCR4, GRIN1, GOT2, and ITGA5 have been identified as the crucial targets correlating with AD. Our findings provide a theoretical framework for understanding the complex molecular mechanisms underlying the effects of MEP on AD and provide insights for the development of prevention and treatment of AD caused by exposure to MEP.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144651712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of MicroRNA Drug Targets for Alzheimer's and Diabetes Mellitus Using Network Medicine.","authors":"Ricardo Castillo-Velázquez, Julio E Castañeda-Delgado, Mariana H García-Hernández, Bruno Rivas-Santiago, Sofia Ruiz-Hernández, Eyra Liliana Ortiz-Pérez, Juan C López-Alvarenga, Gildardo Rivera, Edgar E Lara-Ramírez","doi":"10.2174/0115672050393875250626065205","DOIUrl":"https://doi.org/10.2174/0115672050393875250626065205","url":null,"abstract":"<p><strong>Introduction: </strong>Type 2 diabetes mellitus (T2D) is a known risk factor for developing Alzheimer's disease (AD). Recent research shows that both diseases share complex and related pathophysiological processes. Network medicine approaches can help to elucidate common dysregulated processes among different diseases, such as AD and T2D. Thus, the aim of this work was to determine differentially expressed genes (DEGs) in AD and T2D and to apply a network medicine approach to identify the microRNAs (miRNAs) involved in the AD-T2D association.</p><p><strong>Methods: </strong>Gene expression microarray data sets consisting of 384 control samples and 399 samples belonging to AD and T2D disease were analyzed to obtain DEGs shared by both diseases; the miRNAs associated with these DEGs were predicted using a network medicine approach. Finally, potential small molecules targeting these potentially deregulated miRNAs were identified.</p><p><strong>Results: </strong>AD and T2D shared a small subset of 82 downregulated DEGs. These genes were significantly associated (p < 0.01) with the ontology terms of chemical synaptic deregulation. DEGs were associated with 12 miRNAs expressed in specific tissues for AD and T2D. Such miRNAs were also primarily associated with the ontology terms related to synaptic deregulation and cancer, and AKT signaling pathways. Steroid anti-inflammatory drugs, antineoplastics, and glucose metabolites were predicted to be potential regulators of the 12 shared miRNAs.</p><p><strong>Discussion: </strong>The network medicine approach integrating DEGs and miRNAs enabled the identification of shared, potentially deregulated biological processes and pathways underlying the pathophysiology of AD and T2D. These common molecular mechanisms were also linked to drugs currently used in clinical practice, suggesting that this strategy may inform future drug repurposing efforts. Nonetheless, further in-depth biological validation is required to confirm these findings.</p><p><strong>Conclusion: </strong>Network medicine allowed identifying 12 miRNAs involved in the AD-T2D association, and these could be drug targets for the design of new treatments; however, the identified miRNAs need further experimental confirmation.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144639224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Interaction between Oligodendrocytes and Aβ in Alzheimer's Disease.","authors":"Wenjing Wang, Xueyan Huang, Zucai Xu, Changyin Yu","doi":"10.2174/0115672050401966250625171338","DOIUrl":"https://doi.org/10.2174/0115672050401966250625171338","url":null,"abstract":"<p><p>Oligodendrocytes (OLs) are the primary myelinating cells in the central nervous system (CNS), responsible for maintaining the rapid conduction of nerve signals and ensuring neuronal stability through metabolic and nutritional support. Recent studies have reported that OLs are also involved in the development and progression of Alzheimer's disease (AD), particularly in the production and clearance of amyloid-beta (Aβ), exhibiting complex and critical regulatory functions. While traditional research has predominantly focused on the roles of neurons and microglia in Aβ metabolism, recent evidence indicates that OLs engage in a complex bidirectional interaction with Aβ in AD. On the one hand, OLs can produce Aβ, frequently generating aggregated and highly toxic Aβ42, which contributes to plaque expansion and disease progression. On the other hand, neuronderived Aβ exerts a concentration-dependent dual effect on OLs. At high concentrations, it induces oxidative stress and cell apoptosis, while at low concentrations, it promotes their differentiation and myelin repair functions. Therefore, OLs serve as both a \"source\" and a \"target\" of Aβ production and response, making them a key factor in AD pathogenesis. This review discusses the interaction between OLs and Aβ in AD, aiming to provide new perspectives on targeting OLs for AD therapy. Given the dual role of OLs in Aβ metabolism, targeting OLs dysfunction and the regulatory mechanisms underlying Aβ production and clearance could provide novel therapeutic strategies for AD. Future research should investigate the roles of specific OL populations (including oligodendrocyte precursor cells (OPCs), pre-myelinating OLs, and mature OLs) in Aβ generation and metabolism, focusing on the signaling pathways involved. Additionally, the molecular mechanisms by which OLs regulate other glial cells, such as astrocytes and microglia, through intercellular signaling to facilitate Aβ clearance and maintain neuroglial homeostasis warrant further exploration.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144586051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alterations of Mitophagy (BNIP3), Apoptosis (CASP3), and Autophagy (BECN1) Genes in the Frontal Cortex in an Ischemic Model of Alzheimer's Disease with Long-Term Survival.","authors":"Ryszard Pluta, Janusz Kocki, Anna Bogucka Kocka, Jacek Bogucki, Stanisław J Czuczwar","doi":"10.2174/0115672050385480250619045022","DOIUrl":"https://doi.org/10.2174/0115672050385480250619045022","url":null,"abstract":"<p><strong>Introduction: </strong>Currently, there is no information on changes in the mitophagy (BNIP3), apoptosis (CASP3), and autophagy (BECN1) genes in the frontal cortex after brain ischemia with animal survival for 2 years. Furthermore, it is not known whether the BNIP3, CASP3, and BECN1 genes possess any influence on neurons in the frontal cortex due to ischemia.</p><p><strong>Aim: </strong>The goal of the investigation was to evaluate alterations in the behavior of BNIP3, CASP3, and BECN1 genes in the frontal cortex following ischemia with survival of 2 years.</p><p><strong>Materials and methods: </strong>Gene expression was assessed using an RT-PCR protocol at 2-30 days and 6-24-months after ischemia.</p><p><strong>Results: </strong>BECN1 gene expression after ischemic injury was lower than the controlgroup during 7-30- days and 18 months, whereas overexpression was noted after 2 days, 6-, 12- and 24 months. In the case of BNIP3 gene expression, it was lower than the control group for 2-7 days and higher than the control throughout the remaining time after ischemia. Increased expression of the CASP3 gene was observed except on days 7-30 following ischemia when its expression was lower compared to control values.</p><p><strong>Discussion: </strong>The data seem to indicate that the observed changes in gene expression may reflect the activation and inhibition of different mechanisms involved in the advancement of neurodegeneration after ischemia.</p><p><strong>Conclusion: </strong>Overexpression of BECN1gene is likely to be associated with the induction of neuroprotective phenomena, whereas overexpression of BNIP3 and CASP3 genes can cause harmful effects.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144562532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"History of Senile Dementia from the Antiquity to the Beginning of the Modern Age.","authors":"Francesco Raudino","doi":"10.2174/0115672050387224250615171055","DOIUrl":"https://doi.org/10.2174/0115672050387224250615171055","url":null,"abstract":"<p><strong>Aim: </strong>This study aims, to trace the history of age-associated dementia from the earliest historical periods to the beginning of the modern age.</p><p><strong>Background: </strong>Since the medical literature prior to the early 19th century is relatively scarce, the near absence of senile dementia has been hypothesized.</p><p><strong>Objective: </strong>Verify the prevalence of senile dementia across different historical periods.</p><p><strong>Method: </strong>Beyond the medical literature, reviewed papers addressing legal and social aspects were examined to provide a comprehensive overview of the subject.</p><p><strong>Results: </strong>While the medical literature on the subject is limited, there are a greater abundance of sources discussing social and legislative aspects. The scientific study of dementia had began only in the early 1800s.</p><p><strong>Conclusion: </strong>In ancient times, dementia was not particularly rare, but it was often overlooked, as it was considered an inevitable consequence of aging.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144562533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RESIGN: Alzheimer's Disease Detection Using Hybrid Deep Learning based Res-Inception Seg Network.","authors":"K Amsavalli, S Kanaga Suba Raja, S Sudha","doi":"10.2174/0115672050373821250612053943","DOIUrl":"10.2174/0115672050373821250612053943","url":null,"abstract":"<p><strong>Introduction: </strong>Alzheimer's disease (AD) is a leading cause of death, making early detection critical to improve survival rates. Conventional manual techniques struggle with early diagnosis due to the brain's complex structure, necessitating the use of dependable deep learning (DL) methods. This research proposes a novel RESIGN model is a combination of Res-InceptionSeg for detecting AD utilizing MRI images.</p><p><strong>Methods: </strong>The input MRI images were pre-processed using a Non-Local Means (NLM) filter to reduce noise artifacts. A ResNet-LSTM model was used for feature extraction, targeting White Matter (WM), Grey Matter (GM), and Cerebrospinal Fluid (CSF). The extracted features were concatenated and classified into Normal, MCI, and AD categories using an Inception V3-based classifier. Additionally, SegNet was employed for abnormal brain region segmentation.</p><p><strong>Results: </strong>The RESIGN model achieved an accuracy of 99.46%, specificity of 98.68%, precision of 95.63%, recall of 97.10%, and an F1 score of 95.42%. It outperformed ResNet, AlexNet, Dense- Net, and LSTM by 7.87%, 5.65%, 3.92%, and 1.53%, respectively, and further improved accuracy by 25.69%, 5.29%, 2.03%, and 1.71% over ResNet18, CLSTM, VGG19, and CNN, respectively.</p><p><strong>Discussion: </strong>The integration of spatial-temporal feature extraction, hybrid classification, and deep segmentation makes RESIGN highly reliable in detecting AD. A 5-fold cross-validation proved its robustness, and its performance exceeded that of existing models on the ADNI dataset. However, there are potential limitations related to dataset bias and limited generalizability due to uniform imaging conditions.</p><p><strong>Conclusion: </strong>The proposed RESIGN model demonstrates significant improvement in early AD detection through robust feature extraction and classification by offering a reliable tool for clinical diagnosis.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144334760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advance Nanotechnology-Based Drug Delivery Systems for Alzheimer's Disease: Advancements and Future Perspectives.","authors":"Kuldeep Singh, Jeetendra Kumar Gupta, Gaurav Lakhchora, Divya Jain, Alok Bhatt, Mukesh Chandra Sharma, Mvnl Chaitanya, Mohammad Tabish","doi":"10.2174/0115672050380959250530112247","DOIUrl":"https://doi.org/10.2174/0115672050380959250530112247","url":null,"abstract":"<p><p>Alzheimer's Disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and memory loss, significantly impacting the quality of life for affected individuals. This manuscript explores various innovative therapeutic strategies aimed at enhancing drug delivery to the brain, particularly through the use of nanotechnology. This paper discussed the application of Solid Lipid Nanoparticles (SLNs), dendrimers, and Polymeric Nanoparticles (PNPs) in targeting the Central Nervous System (CNS) to improve bioavailability and therapeutic efficacy. The findings indicate that these advanced delivery systems can enhance brain penetration, reduce Amyloid-Beta (Aβ) deposition, and improve cognitive functions in animal models of AD. Furthermore, the review highlights the challenges associated with these technologies, including limited scalability and potential toxicity, while suggesting future directions for research and development in the field of AD treatment.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144259853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Neuroprotective Potential of Polyphenolic Compounds in Mitigating Quinolinic Acid-Induced Neurotoxicity in Alzheimer's Disease.","authors":"Pallav Gandhi, Shital Panchal","doi":"10.2174/0115672050383383250529100802","DOIUrl":"https://doi.org/10.2174/0115672050383383250529100802","url":null,"abstract":"<p><strong>Background: </strong>Quinolinic Acid (QA), a neurotoxic metabolite in the kynurenine pathway, contributes to neuronal damage, oxidative stress, and neuroinflammation, playing a key role in Alzheimer's Disease (AD) pathogenesis. This study investigates the neuroprotective potential of polyphenolic compounds, particularly lycopene and a Curcumin-Zinc (Cur-Zn) complex, using in- -silico and in-vitro approaches targeting the kynurenine pathway.</p><p><strong>Methodology: </strong>This study evaluated the neuroprotective potential of lycopene and Cur-Zn complex using in-silico and in-vitro approaches. Molecular docking was performed to assess their binding affinities with the kynurenine pathway enzymes, and in-vitro neuroprotection assays on N2a cells measured their efficacy against QA-induced oxidative stress.</p><p><strong>Results: </strong>Docking analysis revealed strong binding affinities of Cur-Zn and lycopene to IDO1 and KMO, with fitness scores of 143.11 and 126.41, respectively, indicating their potential as enzyme- specific inhibitors. Lycopene exhibited the most potent neuroprotective effect (IC50 = 0.63 μM), followed by Cur-Zn (1.59 μM). Both compounds significantly reduced QA-induced ROS levels, as confirmed by DCFDA fluorescence imaging. Additionally, they upregulated KAT and QPRT enzymes, promoting neuroprotective metabolite production.</p><p><strong>Discussion: </strong>Lycopene and Cur-Zn effectively modulate key kynurenine pathway enzymes while mitigating oxidative stress, supporting their potential as neuroprotective agents. Although bisabolol and bromelain exhibited some efficacy, their effects were comparatively lower.</p><p><strong>Conclusion: </strong>Lycopene and Cur-Zn are promising candidates for AD therapy, demonstrating not only anti-oxidant activity but also a capacity to minimise the neurotoxic effects of QA, offering a dual mechanism of action. Further, in-vivo studies are needed to validate their therapeutic potential in neurodegenerative diseases.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144259815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of the Inhibition of AChE and BChE by Carthamus caeruleus Essential Oil and Carline Oxide: Neuroprotective Effects and In Vivo Toxicity Assessment for the Management of Alzheimer's Disease.","authors":"Assia Keniche, Chaimaa Kalache, Mohammed El Amine Dib, Ibtissem El Ouar","doi":"10.2174/0115672050383227250529072253","DOIUrl":"https://doi.org/10.2174/0115672050383227250529072253","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease is associated with dysfunction of the cholinergic system, making the inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) a promising therapeutic approach.</p><p><strong>Objective: </strong>This study aimed to evaluate the neuroprotective effects and toxicity of essential oil (EO) and carlina oxide from Carthamus caeruleus in mice, assessing their potential for Alzheimer's disease treatment.</p><p><strong>Methods: </strong>The chemical composition of the essential oil extracted from the roots of Carthamus caeruleus was analyzed using gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). The main component, carlina oxide, was isolated via column chromatography. The inhibitory activities of AChE and BChE were evaluated in vitro for both the essential oil and carlina oxide. Additionally, in vivo, toxicity was assessed in laboratory mice.</p><p><strong>Results: </strong>Chemical analysis identified carlina oxide (81.6%) as the major constituent, along with minor compounds such as 13-methoxycarlin oxide and hexadecanoic acid. Both the essential oil and its main component, carlina oxide, exhibited significant inhibitory activity against AChE and BChE, enzymes associated with Alzheimer's disease. The essential oil demonstrated promising IC50 values, with stronger anti-BChE activity compared to the reference drug, galantamine. Toxicity tests in mice revealed no adverse effects at lower doses (0.2-0.5 g/kg). However, higher doses (1.0-2.0 g/kg) resulted in mild to significant toxicity, including weight loss and mortality.</p><p><strong>Discussion: </strong>The essential oil and carlina oxide demonstrated potent BChE inhibition, particularly relevant in advanced Alzheimer's disease. While effective at low doses, signs of toxicity were observed at higher concentrations, highlighting the importance of dose optimization. These findings suggest that C. caeruleus may serve as a natural source of cholinesterase inhibitors, pending further in vivo studies and clinical validation.</p><p><strong>Conclusion: </strong>Carthamus caeruleus essential oil and carlina oxide show promising inhibitory effects on AChE and BChE, suggesting their potential as neuroprotective agents. However, their toxicity at higher doses highlights the need for cautious use and further investigation.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144259854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}