Current Alzheimer research最新文献_第8页

Alzheimer's Disease Drug Development. 阿尔茨海默病药物开发。

Current Alzheimer research Pub Date : 2024-01-01 DOI: 10.2174/156720502110250304104224

Leonidas D Panos

引用次数: 0

Visualization Analysis of Tau Protein in the Brain of Alzheimer's Disease: A Scoping Literature Review. 阿尔茨海默病大脑中Tau蛋白的可视化分析：范围文献综述。

Current Alzheimer research Pub Date : 2024-01-01 DOI: 10.2174/0115672050351995241223065923

Dan-Qi Zhang, Xu Yang, Han-Bin Niu, Xu-Chen Sun, Dan-Na Cao, Ang Li, Jin-Huan Yue, Xiao-Ling Li, Qin-Hong Zhang

{"title":"Visualization Analysis of Tau Protein in the Brain of Alzheimer's Disease: A Scoping Literature Review.","authors":"Dan-Qi Zhang, Xu Yang, Han-Bin Niu, Xu-Chen Sun, Dan-Na Cao, Ang Li, Jin-Huan Yue, Xiao-Ling Li, Qin-Hong Zhang","doi":"10.2174/0115672050351995241223065923","DOIUrl":"10.2174/0115672050351995241223065923","url":null,"abstract":"Introduction: This study analyzed the current status, hotspots, and development trends of tau protein research in Alzheimer's disease (AD) and to provide a reference for future research in this field. CiteSpace software was used to scientifically measure and visualize the relevant articles in the field of tau protein in AD brain from the Web of Science Core Collection database from 1991 to 2022.Methods: A total of 568 articles were included, with an exponential growth in the number of articles published from 1991 to 2022, with an average of 17.8 articles per year. The United States is the most productive country in this field, accounting for 46.83% of the total literature. The New York State Institute for Basic Research is the most productive organization, followed by MRC Laboratory Molecular Biology in the UK. The most influential are Kings College London, University of California, San Francisco, and others. Iqbal K is the most productive author.Results: The most productive journal is the Journal of Biological Chemistry, and the journal with the highest impact factor is Acta Neuropathologica. The journal with the highest cumulative impact factor is Nature. The research hotspots mainly focus on the formation and degradation mechanisms of tau protein paired helical filaments and abnormal phosphorylation, AD neurofibrillary tangles and degenerative changes, and model research, mainly involving tau protein abnormal phosphorylation, phosphorylation sites, dephosphorylation, aggregate helical filaments, neurofibrillary tangles mouse models.Conclusion: The research frontier trends mainly focus on the study of pathological changes in tau protein, intervention mechanisms, and the development and practice of clinical therapeutic drugs.","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"649-666"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143124298","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}

引用次数: 0

Nanostructured Lipid Carriers of Donepezil Hydrochloride for the Treatment of Alzheimer's Disease. 用于治疗阿尔茨海默病的盐酸多奈哌齐纳米结构脂质载体。

Current Alzheimer research Pub Date : 2024-01-01 DOI: 10.2174/0115672050288659240229080535

Avinash Tekade, Ram Susar, Gajanan Kulkarni, Samiksha Surwade, Anil Gaikwad

{"title":"Nanostructured Lipid Carriers of Donepezil Hydrochloride for the Treatment of Alzheimer's Disease.","authors":"Avinash Tekade, Ram Susar, Gajanan Kulkarni, Samiksha Surwade, Anil Gaikwad","doi":"10.2174/0115672050288659240229080535","DOIUrl":"10.2174/0115672050288659240229080535","url":null,"abstract":"Background: Alzheimer's Disease (AD) is a long-term brain disorder that worsens over time. A cholinesterase inhibitor called Donepezil HCl (DNZ) is used to treat and control AD. Due to its failure to reach the appropriate concentration in the brain cells, its efficacy upon oral administration is limited, and thus investigation of alternative administration route is necessary.Objective: The objective of this study was to develop donepezil HCl-loaded Nanostructured Lipid Carriers (NLCs) that can bypass the blood-brain barrier and thus be directly delivered to the brain through the nasal route. This method improves availability at the site of action, reduces the negative effects of oral medication, and ensures an expedited commencement of action.Methods: High-pressure homogenization and ultrasonication were used to formulate NLCs. Glyceryl Monostearate (GMS) as a solid lipid, Tween 80 as a surfactant, and Poloxamer 407 as a cosurfactant were used. In this study, argan oil was employed as a liquid lipid as well as a penetration enhancer.Results: The chosen NLCs displayed a particle size of 137.34 ± 0.79 nm, a PDI of 0.365 ± 0.03, and a zeta potential of -10.4 mV. The selected formulation showed an entrapment efficiency of 84.05 ± 1.30% and a drug content of 77.02 ± 0.23%. The concentration of the drug in the brain after intravenous and intranasal administration of DNZ NLCs at 1 h was found to be 0.490 ± 0.007 and 4.287 ± 0.115, respectively. Thus, the concentration of DNZ achieved in the brain after intranasal administration of DNZ NLCs was approximately 9 times more than the concentration when administered by intravenous route.Conclusion: The DNZ-loaded NLCs, when administered via nasal route, showed markedly improved drug availability in the brain, suggesting an efficient drug delivery strategy to treat Alzheimer's disease.","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"710-722"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140041277","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}

引用次数: 0

Age- and Genotype-Dependent Effects of Chronic Nicotine on Presenilin1/2 Double Knockout Mice: From Behavior to Molecular Pathways. 慢性尼古丁对早老素1/2双敲除小鼠的年龄和基因型依赖效应：从行为到分子途径

Current Alzheimer research Pub Date : 2024-01-01 DOI: 10.2174/0115672050363992250127072919

Youwen Si, Bo Meng, Feiyan Qi

{"title":"Age- and Genotype-Dependent Effects of Chronic Nicotine on Presenilin1/2 Double Knockout Mice: From Behavior to Molecular Pathways.","authors":"Youwen Si, Bo Meng, Feiyan Qi","doi":"10.2174/0115672050363992250127072919","DOIUrl":"10.2174/0115672050363992250127072919","url":null,"abstract":"Introduction: The potential therapeutic role of nicotine in Alzheimer's disease (AD) remains controversial, particularly regarding its age-dependent effects and underlying mechanisms.Methods: This study investigated the impact of chronic nicotine administration on cognitive function and molecular pathways in Presenilin 1/2 double knockout (DKO) mice, an amyloid-β: (Aβ:)- independent model of AD. Three-month-old and eight-month-old DKO and wild-type (WT) mice received oral nicotine treatment (100 μg/ml) for three months. Behavioral assessments revealed that while the 6-month-old cohort showed no significant differences between nicotine-treated and control groups regardless of genotype, nicotine improved contextual fear memory in 11-month- old DKO mice but impaired nest-building ability and cued fear memory in age-matched WT controls. Transcriptome analysis of the prefrontal cortex identified distinct molecular responses to nicotine between genotypes.Results: In DKO mice, nicotine modulated neuropeptide signaling and reduced astrocyte activation, while in WT mice, it disrupted cytokine-cytokine receptor interaction and neuroactive ligand- receptor interaction pathways. Western blot analysis revealed that nicotine treatment significantly reduced tau hyperphosphorylation and Glial Fibrillary Acidic Protein (GFAP) expression in 11-month-old DKO mice, which was further confirmed by immunohistochemistry showing decreased astrocyte activation in multiple brain regionsConclusion: These findings demonstrate that nicotine's effects on cognition and molecular pathways are both age- and genotype-dependent, suggesting its therapeutic potential may be limited to specific stages of neurodegeneration while potentially having adverse effects in healthy aging brains.","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"817-832"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143401123","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}

引用次数: 0

Using Entropy as the Convergence Criteria of Ant Colony Optimization and the Application at Gene Chip Data Analysis. 用熵作为蚁群优化的收敛标准及在基因芯片数据分析中的应用

Current Alzheimer research Pub Date : 2024-01-01 DOI: 10.2174/0115672050325388240823092338

Chonghao Gao, Xinping Pang, Chongbao Wang, Jingyue Huang, Hui Liu, Chengjiang Zhu, Kunpei Jin, Weiqi Li, Pengtao Zheng, Zihang Zeng, Yanyu Wei, Chaoyang Pang

{"title":"Using Entropy as the Convergence Criteria of Ant Colony Optimization and the Application at Gene Chip Data Analysis.","authors":"Chonghao Gao, Xinping Pang, Chongbao Wang, Jingyue Huang, Hui Liu, Chengjiang Zhu, Kunpei Jin, Weiqi Li, Pengtao Zheng, Zihang Zeng, Yanyu Wei, Chaoyang Pang","doi":"10.2174/0115672050325388240823092338","DOIUrl":"10.2174/0115672050325388240823092338","url":null,"abstract":"Introduction: When Ant Colony Optimization algorithm (ACO) is adept at identifying the shortest path, the temporary solution is uncertain during the iterative process. All temporary solutions form a solution set.Methods: Where each solution is random. That is, the solution set has entropy. When the solution tends to be stable, the entropy also converges to a fixed value. Therefore, it was proposed in this paper that apply entropy as a convergence criterion of ACO. The advantage of the proposed criterion is that it approximates the optimal convergence time of the algorithm.Results: In order to prove the superiority of the entropy convergence criterion, it was used to cluster gene chip data, which were sampled from patients of Alzheimer's Disease (AD). The clustering algorithm is compared with six typical clustering algorithms. The comparison shows that the ACO using entropy as a convergence criterion is of good quality.Conclusion: At the same time, applying the presented algorithm, we analyzed the clustering characteristics of genes related to energy metabolism and found that as AD occurs, the entropy of the energy metabolism system decreases; that is, the system disorder decreases significantly.","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"324-341"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142305464","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}

引用次数: 0

Association Between Cannabis Use and Subjective Cognitive Decline: Findings from the Behavioral Risk Factor Surveillance System (BRFSS). 大麻使用与主观认知能力下降之间的关系：行为风险因素监测系统（BRFSS）的研究结果。

Current Alzheimer research Pub Date : 2024-01-01 DOI: 10.2174/0115672050301726240219050051

Zhi Chen, Roger Wong

{"title":"Association Between Cannabis Use and Subjective Cognitive Decline: Findings from the Behavioral Risk Factor Surveillance System (BRFSS).","authors":"Zhi Chen, Roger Wong","doi":"10.2174/0115672050301726240219050051","DOIUrl":"10.2174/0115672050301726240219050051","url":null,"abstract":"Background: Cannabis consumption has rapidly increased in the United States due to more states legalizing non-medical and medical use. There is limited research, however, investigating whether cannabis may be associated with cognitive function, particularly across multiple dimensions of cannabis use.Objective: The objective of this study was to examine whether cannabis consumption reason, frequency, and method are associated with subjective cognitive decline (SCD).Methods: Data were obtained from 4,744 U.S. adults aged 45 and older in the 2021 Behavioral Risk Factor Surveillance System (BRFSS). SCD was a self-reported increase in confusion or memory loss in the past year. Odds of SCD by cannabis use reason, frequency, and methods (e.g., smoke, eat, vaporize) were examined using multiple logistic regression after imputing missing data, applying sampling weights, and adjusting for sociodemographic, health, and substance use covariates.Results: Compared to non-users, non-medical cannabis use was significantly associated with 96% decreased odds of SCD (aOR=0.04, 95% CI=0.01-0.44, p<.01). Medical (aOR=0.46, 95% CI=0.06-3.61, p=.46) and dual medical and non-medical use (aOR=0.30, 95% CI=0.03-2.92, p=.30) were also associated with decreased odds of SCD, although not significant. Cannabis consumption frequency and method were not significantly associated with SCD.Conclusion: The reason for cannabis use, but not frequency and method, is associated with SCD. Further research is needed to investigate the mechanisms that may contribute to the observed associations between non-medical cannabis use and decreased odds of SCD.","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"802-810"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139975345","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}

引用次数: 0

Alzheimer's Disease and Suicide: An Integrative Literature Review. 阿尔茨海默病与自杀：综合文献综述》。

Current Alzheimer research Pub Date : 2024-01-01 DOI: 10.2174/0115672050292472240216052614

Juliano Flávio Rubatino Rodrigues, Livia Peregrino Rodrigues, Gerardo Maria de Araújo Filho

引用次数: 0

Research Progress of Mitophagy in Alzheimer's Disease. 阿尔茨海默病中丝粒吞噬作用的研究进展。

Current Alzheimer research Pub Date : 2024-01-01 DOI: 10.2174/0115672050300063240305074310

Jinglin Yao, Bohong Kan, Zhengjia Dong, Zhenyu Tang

引用次数: 0

Current Progress on Central Cholinergic Receptors as Therapeutic Targets for Alzheimer's Disease. 将中枢胆碱能受体作为阿尔茨海默病治疗靶点的最新进展。

Current Alzheimer research Pub Date : 2024-01-01 DOI: 10.2174/0115672050306008240321034006

Kushagra Nagori, Madhulika Pradhan, Mukesh Sharma, Ajazuddin, Hemant R Badwaik, Kartik T Nakhate

{"title":"Current Progress on Central Cholinergic Receptors as Therapeutic Targets for Alzheimer's Disease.","authors":"Kushagra Nagori, Madhulika Pradhan, Mukesh Sharma, Ajazuddin, Hemant R Badwaik, Kartik T Nakhate","doi":"10.2174/0115672050306008240321034006","DOIUrl":"10.2174/0115672050306008240321034006","url":null,"abstract":"Acetylcholine (ACh) is ubiquitously present in the nervous system and has been involved in the regulation of various brain functions. By modulating synaptic transmission and promoting synaptic plasticity, particularly in the hippocampus and cortex, ACh plays a pivotal role in the regulation of learning and memory. These procognitive actions of ACh are mediated by the neuronal muscarinic and nicotinic cholinergic receptors. The impairment of cholinergic transmission leads to cognitive decline associated with aging and dementia. Therefore, the cholinergic system has been of prime focus when concerned with Alzheimer's disease (AD), the most common cause of dementia. In AD, the extensive destruction of cholinergic neurons occurs by amyloid-β plaques and tau protein-rich neurofibrillary tangles. Amyloid-β also blocks cholinergic receptors and obstructs neuronal signaling. This makes the central cholinergic system an important target for the development of drugs for AD. In fact, centrally acting cholinesterase inhibitors like donepezil and rivastigmine are approved for the treatment of AD, although the outcome is not satisfactory. Therefore, identification of specific subtypes of cholinergic receptors involved in the pathogenesis of AD is essential to develop future drugs. Also, the identification of endogenous rescue mechanisms to the cholinergic system can pave the way for new drug development. In this article, we discussed the neuroanatomy of the central cholinergic system. Further, various subtypes of muscarinic and nicotinic receptors involved in the cognition and pathophysiology of AD are described in detail. The article also reviewed primary neurotransmitters that regulate cognitive processes by modulating basal forebrain cholinergic projection neurons.","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"50-68"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140290125","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}

引用次数: 0

Beyond Conventional Therapies: Molecular Dynamics of Alzheimer's Treatment through CLOCK/BMAL1 Interactions. 超越传统疗法：通过 CLOCK/BMAL1 相互作用治疗阿尔茨海默氏症的分子动力学。

Current Alzheimer research Pub Date : 2024-01-01 DOI: 10.2174/0115672050301014240315065235

Ismail Celil Haskologlu, Emine Erdag, Ahmet Ozer Sehirli, Orhan Uludag, Nurettin Abacioglu

{"title":"Beyond Conventional Therapies: Molecular Dynamics of Alzheimer's Treatment through CLOCK/BMAL1 Interactions.","authors":"Ismail Celil Haskologlu, Emine Erdag, Ahmet Ozer Sehirli, Orhan Uludag, Nurettin Abacioglu","doi":"10.2174/0115672050301014240315065235","DOIUrl":"10.2174/0115672050301014240315065235","url":null,"abstract":"Background: Alzheimer's Disease (AD) represents a neurodegenerative disorder characterized by cognitive and behavioral impairments significantly hindering social and occupational functioning. Melatonin, a hormone pivotal in regulating the body's intrinsic circadian rhythm, also acts as a catalyst in the breakdown of beta-amyloid deposits, offering a promising therapeutic approach for AD. The upregulation of Brain and Muscle ARNT-Like 1 (Bmal1) gene expression, stimulated by melatonin, emerges as a potential contributor to AD intervention. Current pharmacological interventions, such as FDA-approved cholinesterase inhibitors and the recently authorized monoclonal antibody, Lecanemab, are utilized in AD management. However, the connection between these medications and Bmal1 remains insufficiently explored.Objective: This study aims to investigate the molecular effects of FDA-endorsed drugs on the CLOCK: Bmal1 dimer. Furthermore, considering the interactions between melatonin and Bmal1, this research explores the potential synergistic efficacy of combining these pharmaceutical agents with melatonin for AD treatment.Methods: Using molecular docking and MM/PBSA methodologies, this research determines the binding affinities of drugs within the Bmal1 binding site, constructing interaction profiles.Results: The findings reveal that, among FDA-approved drugs, galanthamine and donepezil demonstrate notably similar binding energy values to melatonin, interacting within the Bmal1 binding site through analogous amino acid residues and functional groups.Conclusion: A novel therapeutic approach emerges, suggesting the combination of melatonin with Lecanemab as a monoclonal antibody therapy. Importantly, prior research has not explored the effects of FDA-approved drugs on Bmal1 expression or their potential for synergistic effects.","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"862-874"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140178533","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}

引用次数: 0