scholarly journals Common SAR Derived from Linear and Non-linear QSAR Studies on AChE Inhibitors used in the Treatment of Alzheimer's Disease

2017 ◽  
Vol 15 (8) ◽  
Author(s):  
Babitha Pallikkara Pulikkal ◽  
Sahila Mohammed Marunnan ◽  
Srinivas Bandaru ◽  
Mukesh Yadav ◽  
Anuraj Nayarisseri ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Qsar Studies ◽  
Ache Inhibitors ◽  
Non Linear

scholarly journals QSAR Studies on N-aryl Derivative Activity Towards Alzheimer’s Disease

Molecules ◽  
2009 ◽  
Vol 14 (4) ◽  
pp. 1448-1455 ◽  
Author(s):  
Kamalakaran Anand Solomon ◽  
Srinivasan Sundararajan ◽  
Veluchamy Abirami
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Qsar Studies ◽  
Aryl Derivative

scholarly journals FMRI Functional Connectivity Evaluation in Alzheimer’s Stages: Linear and Non-Linear Approaches

2021 ◽  
Author(s):  
Hessam Ahmadi ◽  
Emad Fatemizadeh ◽  
Ali Motie Nasrabadi
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Functional Connectivity ◽  
Permutation Test ◽  
Pearson Correlation ◽  
Functional Integration ◽  
Clustering Coefficient ◽  
Kernel Trick ◽  
Non Linear ◽  
The Brain

Abstract Neuroimaging data analysis reveals the underlying interactions in the brain. It is essential, yet controversial, to choose a proper tool to manifest brain functional connectivity. In this regard, researchers have not reached a definitive conclusion between the linear and non-linear approaches, as both have pros and cons. In this study, to evaluate this concern, the functional Magnetic Resonance Imaging (fMRI) data of different stages of Alzheimer’s disease are investigated. In the linear approach, the Pearson Correlation Coefficient (PCC) is employed as a common technique to generate brain functional graphs. On the other hand, for non-linear approaches, two methods including Distance Correlation (DC) and the kernel trick are utilized. By the use of the three mentioned routines and graph theory, functional brain networks of all stages of Alzheimer’s disease (AD) are constructed and then sparsed. Afterwards, graph global measures are calculated over the networks and a non-parametric permutation test is conducted. Results reveal that the non-linear approaches have more potential to discriminate groups in all stages of AD. Moreover, the kernel trick method is more powerful in comparison to the DC technique. Nevertheless, AD degenerates the brain functional graphs more at the beginning stages of the disease. At the first phase, both functional integration and segregation of the brain degrades, and as AD progressed brain functional segregation further declines. The most distinguishable feature in all stages is the clustering coefficient that reflects brain functional segregation.

The ABC of Alzheimer's Disease: Behavioral Symptoms and Their Treatment

2002 ◽  
Vol 14 (S1) ◽  
pp. 27-49 ◽  
Author(s):  
George T. Grossberg
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Treatment Options ◽  
Lewy Body Dementia ◽  
Economic Cost ◽  
Brain Regions ◽  
Behavioral Symptoms ◽  
Psychotic Symptoms ◽  
Ache Inhibitors ◽  
Che Inhibitors

Behavioral and psychological symptoms of dementia (BPSD) are a common manifestation of Alzheimer's disease (AD) and other dementia syndromes. Patients experience prominent and multiple symptoms, which are both distressing and a source of considerable social, health, and economic cost. Development of symptoms is in part related to progressive neurodegeneration and cholinergic deficiency in brain regions important in the regulation of behavioral and emotional responses including the cortex, hippocampus, and limbic system. Cholinesterase (ChE) inhibitors offer a mechanism-based approach to therapy to enhance endogenous cholinergic neurotransmission. Studies using ChE inhibitors have demonstrated their clear potential to improve or stabilize existing BPSD. Differences have been noted between selective acetylcholinesterase (AChE) inhibitors (donepezil and galantamine) and dual ChE inhibitors (rivastigmine) in terms of treatment response. While donepezil has shown efficacy in moderate to severe noninstitutionalized AD patients, conflicting results have been obtained in mild to moderate patients and in nursing home patients. Galantamine has been shown to delay the onset of BPSD during a five-month study but has been otherwise poorly studied to-date. Both donepezil and galantamine have not as yet demonstrated efficacy in reducing psychotic symptoms or in reducing levels of concomitant psychotropic medication use. Studies with the dual ChE inhibitor rivastigmine in mild to moderately severe AD and in Lewy body dementia (LBD) have shown improvements in behavioral symptoms including psychosis. Improvements have been maintained over a period of up to two years. In addition, institutionalized patients with severe AD have shown symptomatic benefits with a reduction in the requirement for additional psychotropic drugs following treatment with rivastigmine. The psychotropic properties associated with rivastigmine may in part be mediated through effects on butyrylcholinesterase. Current treatment options are limited for patients with dementia syndromes other than AD. However, data concerning rivastigmine in patients with LBD and preliminary studies in Parkinson's disease dementia and vascular dementia suggest a role for ChE inhibitors across the spectrum of dementia syndromes. Finally, studies that incorporated a delayed start design demonstrate that ChE inhibitors may delay the progression of BPSD.

scholarly journals Influence of Acetylcholinesterase Inhibitors Used in Alzheimer’s Disease Treatment on the Activity of Antioxidant Enzymes and the Concentration of Glutathione in THP-1 Macrophages under Fluoride-Induced Oxidative Stress

2018 ◽  
Vol 16 (1) ◽  
pp. 10 ◽  
Author(s):  
Marta Goschorska ◽  
Izabela Gutowska ◽  
Irena Baranowska-Bosiacka ◽  
Katarzyna Piotrowska ◽  
Emilia Metryka ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Reactive Oxygen Species ◽  
Alzheimer's Disease ◽  
Antioxidant Enzymes ◽  
Antioxidant Properties ◽  
Reactive Oxygen ◽  
Acetylcholinesterase Inhibitors ◽  
Oxygen Species ◽  
Ache Inhibitors

It has been reported that donepezil and rivastigmine, the acetylcholinesterase (AchE) inhibitors commonly used in the treatment of Alzheimer’s disease (AD), do not only inhibit AChE but also have antioxidant properties. As oxidative stress is involved in AD pathogenesis, in our study we attempted to examine the influence of donepezil and rivastigmine on the activity of antioxidant enzymes and glutathione concentration in macrophages—an important source of reactive oxygen species and crucial for oxidative stress progression. The macrophages were exposed to sodium fluoride induced oxidative stress. The antioxidant enzymes activity and concentration of glutathione were measured spectrophotometrically. The generation of reactive oxygen species was visualized by confocal microscopy. The results of our study showed that donepezil and rivastigmine had a stimulating effect on catalase activity. However, when exposed to fluoride-induced oxidative stress, the drugs reduced the activity of some antioxidant enzymes (Cat, SOD, GR). These observations suggest that the fluoride-induced oxidative stress may suppress the antioxidant action of AChE inhibitors. Our results may have significance in the clinical practice of treatment of AD and other dementia diseases.

Virtual Screening in Chinese Herbs with Multi-Target Effect on Alzheimer's Disease

2013 ◽  
Vol 765-767 ◽  
pp. 256-260
Author(s):  
Yan Ling Zhang ◽  
Yuan Ming Wang ◽  
Yan Jiang Qiao
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Virtual Screening ◽  
Glycogen Synthase ◽  
Chinese Herbs ◽  
Multiple Targets ◽  
Active Compounds ◽  
Ache Inhibitors ◽  
Gsk 3Β ◽  
Pharmacophore Models

Multiple targets which closely related to Alzheimer's disease (AD) pathogenesis were selected for pharmacophore models generation and virtual screening in Chinese herbs. The targets comprised Acetylcholinesterase (AchE), muscarinic receptor 1 (M1), γ-secretase and glycogen synthase kinase 3β (GSK-3β). The pharmacophore models, which of AchE inhibitors, M1 agonists, γ-secretase inhibitors and GSK-3β inhibitors, were constructed by distance comparison method. Four testing databases for the evaluation of pharmacophore models were constructed with the active compounds with clearly marked activity on each target. The metric CAI (Comprehensive Appraisal Index) was then used to evaluate and obtain the best pharmacophore models of each target, which were then applied to screen the Traditional Chinese Medicine Database for potential active compounds in Chinese herbs. Four common used herbs were obtained, which contain the active compounds and can act on multiple targets, and were expected to have multiple activity of anti-AD disease.

Identification of Human Acetylcholinesterase Inhibitors from the Constituents of EGb761 by Modeling Docking and Molecular Dynamics Simulations

2018 ◽  
Vol 21 (1) ◽  
pp. 41-49 ◽  
Author(s):  
Lihu Zhang ◽  
Dongdong Li ◽  
Fuliang Cao ◽  
Wei Xiao ◽  
Linguo Zhao ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Docking ◽  
Serine Proteases ◽  
Colorimetric Method ◽  
Acetylcholinesterase Inhibitors ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Ache Inhibitors ◽  
Starting Point

Aim and Objective: EGb761, a standardized and well-defined product extract of Ginkgo biloba leaves, has beneficial role in the treatment of multiple diseases, particularly Alzheimer's disease (AD). Identification of natural acetylcholinesterase (AChE) inhibitors from EGb761 would provide a novel therapeutic approach against the Alzheimer's disease. Material and Method: A series of 21 kinds of promising EGb761 compounds were selected, and subsequently evaluated for their potential ability to bind AChE enzyme by molecular docking and a deep analysis of protein surface pocket features. Results: Docking results indicated that these compounds can bind tightly with the active site of human AChE, with favorable distinct interactions around several important residues Asp74, Leu289, Phe295, Ser293, Tyr341, Trp286 and Val294 in the active pocket. Most EGB761 compounds could form the hydrogen bond interactions with the negatively charged Asp74 and Phe295 residues. Among these compounds, diosmetin is the one with the best-predicted docking score while three key hydrogen bonds can be formed between small molecule and corresponding residues of the binding site. Besides, other three compounds luteolin, apigenin, and isorhamnetin have better predicted docking scores towards AChE than other serine proteases, i.e Elastase, Tryptase, Factor XA, exhibiting specificity for AChE inhibition. The RMSD and MM-GBSA results from molecular dymamic simulations indicated that the docking pose of diosmetin-AChE complex displayed highly stable, which can be used for validating the accuracy of molecular docking study. Subsequently, the AChE inhibitory activities of these compounds were evaluated by the Ellman's colorimetric method. Conclusion: The obtained results revealed that all the four compounds exhibited modest AChE inhibitory activity, among which Diosmetin manifested remarkable anti-AChE activity, comparable with the reference compound, Physostigmine. It can be deduced that these EGB761 compounds can be regarded as a promising starting point for developing AChE inhibitors against AD.

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