Current Alzheimer research最新文献_第2页

Comprehensive Investigation of Natural Ligands as Inhibitors of β Secretase to Identify Alzheimer's Disease Therapeutics. 全面研究作为β分泌酶抑制剂的天然配体，以确定阿尔茨海默氏症治疗药物。

Current Alzheimer research Pub Date : 2024-07-15 DOI: 10.2174/0115672050323622240705043337

Shikha Kushwah, Ashutosh Mani

{"title":"Comprehensive Investigation of Natural Ligands as Inhibitors of β Secretase to Identify Alzheimer's Disease Therapeutics.","authors":"Shikha Kushwah, Ashutosh Mani","doi":"10.2174/0115672050323622240705043337","DOIUrl":"https://doi.org/10.2174/0115672050323622240705043337","url":null,"abstract":"Introduction: Alzheimer's disease (AD) is an alarmingly prevalent worldwide neurological disorder that affects millions of people and has severe effects on cognitive functions. The amyloid hypothesis, which links AD to Aβ (amyloid beta) plaque aggregation, is a well-acknowledged theory. The β-secretase (BACE1) is the main cause of Aβ production, which makes it a possible target for therapy. FDA-approved therapies for AD do exist, but none of them explicitly target BACE1, and their effectiveness is constrained and accompanied by adverse effects.Materials and methods: We determined the essential chemical components of medicinal herbs by conducting a thorough literature research for BACE1. Computational methods like molecular docking, ADMET (Absorption, distribution, metabolism, excretion, toxicity) screening, molecular dynamic simulations, and MMPBSA analysis were performed in order to identify the most promising ligands for β-secretase.Results: The results suggested that withasomniferol, tinosporide, and curcumin had better binding affinity with BACE1, suggesting their potential as therapeutic candidates against Alzheimer's disease.Conclusion: Herbal therapeutics have immense applications in the treatment of chronic diseases like Alzheimer's disease, and there is an urgent need to assess their efficacy as therapeutics.","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141636393","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 : 2024-03-05 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":"https://doi.org/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.Method: 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 co-- surfactant 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":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-05","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

Exploring Potential of Nano-formulations in the Treatment of Alzheimer's Disease through Nasal Route. 探索纳米制剂通过鼻腔途径治疗阿尔茨海默病的潜力。

Current Alzheimer research Pub Date : 2024-02-29 DOI: 10.2174/0115672050290462240222092303

Avinash Tekade, Prasad Kadam, Sachin Jagdale, Samiksha Surwade, Anil Gaikwad, Parth Pawar, Rushikesh Shinde

{"title":"Exploring Potential of Nano-formulations in the Treatment of Alzheimer's Disease through Nasal Route.","authors":"Avinash Tekade, Prasad Kadam, Sachin Jagdale, Samiksha Surwade, Anil Gaikwad, Parth Pawar, Rushikesh Shinde","doi":"10.2174/0115672050290462240222092303","DOIUrl":"https://doi.org/10.2174/0115672050290462240222092303","url":null,"abstract":"Objective: Alzheimer's disease, a progressive neurodegenerative disorder, severely impacts cognitive function and daily living. The current treatment provides only symptomatic relief, and thus, disease-modifying therapies targeting underlying causes are needed. Although several potential therapies are in various stages of clinical trials, bringing a new Alzheimer's drug to market remains challenging. Hence, researchers are also exploring monoclonal antibodies, tau protein inhibitors, and anti-inflammatory drugs as treatment options. Conventionally designed dosage forms come with limitations like poor absorption, first-pass metabolism, and low bioavailability. They also cause systemic adverse effects because these designed systems do not provide target- specific drug delivery. Thus, in this review, the authors highlighted the current advancements in the development of intranasal nanoformulations for the treatment of Alzheimer's disease. This strategy of delivering anti-Alzheimer drugs through the nasal route may help to target the drug exactly to the brain, achieve rapid onset of action, avoid first-pass metabolism, and reduce the side effects and dose required for administration.Conclusion: Delivering drugs to the brain through the nasal route for treating Alzheimer's disease is crucial due to the limited efficacy of existing treatments and the profound impact of the disease on patients and their families. Thus, by exploring innovative approaches such as nose-to-brain drug delivery, it is possible to improve the quality of life for individuals living with Alzheimer's and alleviate its societal burden.","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139998796","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

A Look at the Etiology of Alzheimer's Disease based on the Brain Ischemia Model. 基于脑缺血模型的阿尔茨海默病病因分析

Current Alzheimer research Pub Date : 2024-01-01 DOI: 10.2174/0115672050320921240627050736

Ryszard Pluta

{"title":"A Look at the Etiology of Alzheimer's Disease based on the Brain Ischemia Model.","authors":"Ryszard Pluta","doi":"10.2174/0115672050320921240627050736","DOIUrl":"10.2174/0115672050320921240627050736","url":null,"abstract":"Alzheimer's disease (AD) is the frequent form of dementia in the world. Despite over 100 years of research into the causes of AD, including amyloid and tau protein, the research has stalled and has not led to any conclusions. Moreover, numerous projects aimed at finding a cure for AD have also failed to achieve a breakthrough. Thus, the failure of anti-amyloid and anti-tau protein therapy to treat AD significantly influenced the way we began to think about the etiology of the disease. This situation prompted a group of researchers to focus on ischemic brain episodes, which, like AD, mostly present alterations in the hippocampus. In this context, it has been proposed that cerebral ischemic incidents may play a major role in promoting amyloid and tau protein in neurodegeneration in AD. In this review, we summarized the experimental and clinical research conducted over several years on the role of ischemic brain episodes in the development of AD. Studies have shown changes typical of AD in the course of brain neurodegeneration post-ischemia, i.e., progressive brain and hippocampal atrophy, increased amyloid production, and modification of tau protein. In the post-ischemic brain, the diffuse and senile amyloid plaques and the development of neurofibrillary tangles characteristic of AD were revealed. The above data evidently showed that after brain ischemia, there are modifications in protein folding, leading to massive neuronal death and damage to the neuronal network, which triggers dementia with the AD phenotype.","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"166-182"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141500104","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

Advances in Developing Small Molecule Drugs for Alzheimer's Disease. 开发治疗阿尔茨海默病小分子药物的进展。

Current Alzheimer research Pub Date : 2024-01-01 DOI: 10.2174/0115672050329828240805074938

Wei Zhang, Liujie Zhang, Mingti Lv, Yun Fu, Xiaowen Meng, Mingyong Wang, Hecheng Wang

引用次数: 0

Dysregulation of Porphyromonas gingivalis Agmatine Deiminase Expression in Alzheimer's Disease. 阿尔茨海默病中牙龈卟啉菌阿加明脱氨酶的表达失调

Current Alzheimer research Pub Date : 2024-01-01 DOI: 10.2174/0115672050327009240808103542

Asma Hamdi, Sana Baroudi, Alya Gharbi, Wafa Babay, Ahmed Baligh Laaribi, Imene Kacem, Saloua Mrabet, Ines Zidi, Naouel Klibi, Riadh Gouider, Hadda-Imene Ouzari

{"title":"Dysregulation of Porphyromonas gingivalis Agmatine Deiminase Expression in Alzheimer's Disease.","authors":"Asma Hamdi, Sana Baroudi, Alya Gharbi, Wafa Babay, Ahmed Baligh Laaribi, Imene Kacem, Saloua Mrabet, Ines Zidi, Naouel Klibi, Riadh Gouider, Hadda-Imene Ouzari","doi":"10.2174/0115672050327009240808103542","DOIUrl":"10.2174/0115672050327009240808103542","url":null,"abstract":"Background: Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder, with a significant burden on global health. AD is characterized by a progressive cognitive decline and memory loss. Emerging research suggests a potential link between periodontitis, specifically the presence of oral bacteria such as Porphyromonas gingivalis (P. gingivalis), and AD progression. P. gingivalis produces an enzyme, Agmatine deiminase (AgD), which converts agmatine to N-carbamoyl putrescine (NCP), serving as a precursor to essential polyamines. Recent studies have confirmed the correlation between disruptions in polyamine metabolism and cognitive impairment.Objective: This study aims to investigate the dysregulation of P. gingivalis Agmatine deiminase (PgAgD) in the context of AD.Methods: Saliva samples were collected from a total of 54 individuals, including 27 AD patients and 27 healthy controls. The expression of the PgAgD gene was analyzed using quantitative Real-- Time PCR.Results: The results showed a significant decrease in PgAgD gene expression in the saliva samples of AD patients compared to healthy controls. This downregulation was found in AD patients with advanced stages of periodontitis. Additionally, a correlation was observed between the decrease in PgAgD expression and the 30-item Mini-Mental State Examination (MMSE) score.Conclusion: These findings suggest that measuring PgAgD expression in saliva could be a noninvasive tool for monitoring AD progression and aid in the early diagnosis of patients with periodontitis. Further research is needed to validate our results and explore the underlying mechanisms linking periodontitis, PgAgD expression, and AD pathophysiology.","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"232-241"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141984241","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

"Cyclophilin A" Enzymatic Effect on the Aggregation Behavior of 1N4R Tau Protein: An Overlooked Crucial Determinant that should be Re-considered in Alzheimer's Disease Pathogenesis. "嗜环蛋白 A "对 1N4R Tau 蛋白聚集行为的酶促作用：阿尔茨海默病发病机制中应重新考虑的一个被忽视的关键决定因素

Current Alzheimer research Pub Date : 2024-01-01 DOI: 10.2174/0115672050330163240812050223

Samira Ranjbar, Masomeh Mehrabi, Vali Akbari, Somayeh Pashaei, Reza Khodarahmi

{"title":"\"Cyclophilin A\" Enzymatic Effect on the Aggregation Behavior of 1N4R Tau Protein: An Overlooked Crucial Determinant that should be Re-considered in Alzheimer's Disease Pathogenesis.","authors":"Samira Ranjbar, Masomeh Mehrabi, Vali Akbari, Somayeh Pashaei, Reza Khodarahmi","doi":"10.2174/0115672050330163240812050223","DOIUrl":"10.2174/0115672050330163240812050223","url":null,"abstract":"Background: Neurodegenerative disorders like Alzheimer's disease (AD) involve the abnormal aggregation of tau protein, which forms toxic oligomers and amyloid deposits. The structure of tau protein is influenced by the conformational states of distinct proline residues, which are regulated by peptidyl-prolyl isomerases (PPIases). However, there has been no research on the impact of human cyclophilin A (CypA) as a PPIase on (non-phosphorylated) tau protein aggregation.Methods: On the basis of these explanations, we used various spectroscopic techniques to explore the effects of CypA on tau protein aggregation behavior.Results: We demonstrated the role of the isomerization activity of CypA in promoting the formation of tau protein amyloid fibrils with well-defined and highly ordered cross-β structures. According to the \"cistauosis hypothesis,\" CypA's ability to enhance tau protein fibril formation in AD is attributed to the isomerization of specific proline residues from the trans to cis configuration. To corroborate this theory, we conducted refolding experiments using lysozyme as a model protein. The presence of CypA increased lysozyme aggregation and impeded its refolding process. It is known that proper refolding of lysozyme relies on the correct (trans) isomerization of two critical proline residues.Conclusion: Thus, our findings confirmed that CypA induces the trans-to-cis isomerization of specific proline residues, ultimately leading to increased aggregation. Overall, this study highlights the emerging role of isomerization in tau protein pathogenesis in AD.","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"242-257"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142006213","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

Morphometric Analysis of Corpus Callosum in Individuals with Alzheimer's Disease: Magnetic Resonance Imaging (MRI) Study. 阿尔茨海默氏症患者胼胝体的形态计量分析：磁共振成像（MRI）研究。

Current Alzheimer research Pub Date : 2024-01-01 DOI: 10.2174/0115672050335744240820065952

Musa Acar, Sultan Uğur

引用次数: 0

Drive My CAR-AD Research here, there and Everywhere. Drive My CAR-AD Research here, there and Everywhere.

Current Alzheimer research Pub Date : 2024-01-01 DOI: 10.2174/156720502101240524145811

Juan Manuel Górriz Sáez

引用次数: 0

Exploring the Therapeutic Potential of 8-Prenyldaidzein: A Comprehensive Study of its Multi-Target Efficacy in Alzheimer's Disease. 8-丙烯基大豆苷元治疗阿尔茨海默病的多靶点疗效综合研究

Current Alzheimer research Pub Date : 2024-01-01 DOI: 10.2174/0115672050358848241211080546

Kunal Bhattacharya, Dalakamon Sungoh, Daphilari Kharmujai, Ashraful Islam, Dibyajyoti Das, Saurav Kumar Jha, Nongmaithem Randhoni Chanu, Bhaswati Kashyap, Nilutpal Sharma Bora, Bhargab Jyoti Sahariah, Satyendra Deka, Pukar Khanal

{"title":"Exploring the Therapeutic Potential of 8-Prenyldaidzein: A Comprehensive Study of its Multi-Target Efficacy in Alzheimer's Disease.","authors":"Kunal Bhattacharya, Dalakamon Sungoh, Daphilari Kharmujai, Ashraful Islam, Dibyajyoti Das, Saurav Kumar Jha, Nongmaithem Randhoni Chanu, Bhaswati Kashyap, Nilutpal Sharma Bora, Bhargab Jyoti Sahariah, Satyendra Deka, Pukar Khanal","doi":"10.2174/0115672050358848241211080546","DOIUrl":"10.2174/0115672050358848241211080546","url":null,"abstract":"Background: Alzheimer's disease (AD) is marked by cognitive decline, amyloid plaques, neurofibrillary tangles, and cholinergic loss. Due to the limited success of amyloid-targeted therapies, attention has shifted to new non-amyloid targets like phosphodiesterases (PDE). This study investigates the potential of Flemingia vestita (FV) phytomolecules and derivatives, particularly 8-Prenyldaidzein, in AD treatment.Materials and methods: Phytocompounds and derivatives were screened for drug-likeness, toxicity, BBB permeability, and ADME profiles. Molecular docking was conducted with PDE5A, BACE-1, and AChE, followed by molecular dynamics (MD) simulations on the best binding complexes.Results: 8-Prenyldaidzein, a derivative of daidzein, demonstrated favorable drug-likeness and ADME properties. It exhibited strong binding to PDE5A, BACE-1, and AChE, with MD simulations confirming stable protein-ligand interactions.Discussion: The multi-target potential of 8-Prenyldaidzein, particularly through non-amyloid pathways, offers a promising approach to AD therapy. Its inhibition of PDE5A, BACE-1, and AChE could address multiple aspects of AD pathology.Conclusion: 8-Prenyldaidzein shows strong potential as a multi-target inhibitor for AD treatment. While in-silico findings are promising, further experimental validation is needed to confirm its clinical applicability.","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"578-598"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142884013","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