Acetylcholinesterase Inhibitors in the Treatment of Neurodegenerative Diseases and the Role of Acetylcholinesterase in their Pathogenesis

Walczak-Nowicka, Łucja Justyna; Herbet, Mariola

doi:10.3390/ijms22179290

Cited by 119 publications

(85 citation statements)

References 539 publications

(569 reference statements)

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“…DPP4 inhibitors have been shown to control blood glucose levels and prevent the exacerbation of cognitive impairment in older type 2 diabetes patients with mild cognitive impairment [ 52 ]. Acetylcholinesterase (AChE) is involved in inflammatory reactions, neuronal apoptosis, oxidative stress and the aggregation of pathological proteins, which are closely related to the pathogenesis of neurodegenerative diseases [ 53 ]. Studies have shown that low doses of donepezil (2.5 mg/d) can improve cognitive function, especially memory function, in patients with aMCI [ 54 ].…”

Section: Discussionmentioning

confidence: 99%

Medication Rules in Herbal Medicine for Mild Cognitive Impairment: A Network Pharmacology and Data Mining Study

Chang

Wang

Tian

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Background. Although traditional Chinese medicine (TCM) has good efficacy in the treatment of mild cognitive impairment (MCI), especially memory improvement and safety, its substance basis and intervention mechanism are particularly complex and unknown. Therefore, based on network pharmacology and data mining, this study aims to explore the rules, active ingredients and mechanism of TCM in the treatment of MCI. Methods. By searching the GeneCard, OMIM, DisGeNET and DrugBank databases, we obtained the critical targets associated with MCI. We matched the components and herbs corresponding to the important targets in the TCMSP platform. Using Cytoscape 3.7.2 software, we constructed a target-component-herb network and conducted a network topology analysis to obtain the core components and herbs. Molecular docking was used to preliminarily analyze and predict the binding activities and main binding combinations of the core targets and components. Based on the analysis of the properties, flavor and meridian distribution of herbs, the rules of herbal therapy for MCI were summarized. Results. Twenty-eight critical targets were obtained after the screening. Using the TCMSP platform, 492 components were obtained. After standardization, we obtained 387 herbs. Based on the target-composition-herb network analysis, the core targets were ADRB2, ADRA1B, DPP4, ACHE and ADRA1D. According to the screening, the core ingredients were beta-sitosterol, quercetin, kaempferol, stigmasterol and luteolin. The core herbs were matched to Danshen, Yanhusuo, Gancao, Gouteng and Jiangxiang. It was found that the herbs were mainly warm in nature, pungent in taste and liver and lung in meridian. The molecular docking results showed that most core components exhibited strong binding activity to the target combination regardless of the in or out of network combination. Conclusion. The results of this study indicate that herbs have great potential in the treatment of MCI. This study provides a reference and basis for clinical application, experimental research and new drug development of herbal therapy for MCI.

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Section: Discussionmentioning

confidence: 99%

Medication Rules in Herbal Medicine for Mild Cognitive Impairment: A Network Pharmacology and Data Mining Study

Chang

Wang

Tian

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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“…Neurodegenerative diseases can include Alzheimer’s Disease (AD), PD, and multiple sclerosis (MS) [ 147 , 148 , 149 , 150 ]. These diseases usually lead to the degeneration of the nervous system by different mechanisms depending on the disease.…”

Section: Beneficial Properties Of Sodium Benzoatementioning

confidence: 99%

Sodium Benzoate—Harmfulness and Potential Use in Therapies for Disorders Related to the Nervous System: A Review

Walczak-Nowicka

Herbet

2022

Nutrients

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Currently, due to the large number of reports regarding the harmfulness of food additives, more and more consumers follow the so-called “clean label” trend, i.e., prefer and choose the least-processed food products. One of the compounds known as a preservative with a high safety profile is sodium benzoate. While some studies show that it can be used to treat conditions such as depression, pain, schizophrenia, autism spectrum disorders, and neurodegenerative diseases, others report its harmfulness. For example, it was found to cause mutagenic effects, generate oxidative stress, disrupt hormones, and reduce fertility. Due to such disparate results, the purpose of this study is to comprehensively discuss the safety profile of sodium benzoate and its potential use in neurodegenerative diseases, especially in autism spectrum disorder (ASD), schizophrenia, major depressive disorder (MDD), and pain relief.

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“…As shown in Table 6, compound 1 seems to be the most active on the nervous system by targeting key enzymes named acetylcholinesterase (Pa = 0.292) and butyrylcholinesterase (Pa = 0.219) in a non-negligible way, which suggests that this compound could actively participate in the regulation of the activity of these two enzymes known for their important roles in cholinergic transmission by facilitating the hydrolysis of acetylcholine (ACh) neurotransmitter [103]. On the other hand, compound 1 may also participate with other compounds ina synergistic way to limit the activity of these enzymes, since an excessive activity of acetylcholinesterase may lead in the long term to neurodegenerative illnesses such as Alzheimer's and Parkinson's diseases [104]. A key receptor called muscarinic acetylcholine receptor (M1) could be also targeted by this compound (Pa = 0.175), and several studies [105,106] reported the crucial role of this receptor during learning and memory processes, but it could also be a promising therapeutic target for the improvement of cognitive decline in Alzheimer's disease (AD).…”

Section: Macromolecular Targets Predictionmentioning

confidence: 99%

In Silico Investigation of Some Compounds from the N-Butanol Extract of Centaurea tougourensis Boiss. & Reut.

et al. 2022

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Bioinformatics as a newly emerging discipline is considered nowadays a reference to characterize the physicochemical and pharmacological properties of the actual biocompounds contained in plants, which has helped the pharmaceutical industry a lot in the drug development process. In this study, a bioinformatics approach known as in silico was performed to predict, for the first time, the physicochemical properties, ADMET profile, pharmacological capacities, cytotoxicity, and nervous system macromolecular targets, as well as the gene expression profiles, of four compounds recently identified from Centaurea tougourensis via the gas chromatography–mass spectrometry (GC–MS) approach. Thus, four compounds were tested from the n-butanol (n-BuOH) extract of this plant, named, respectively, Acridin-9-amine, 1,2,3,4-tetrahydro-5,7-dimethyl- (compound 1), 3-[2,3-Dihydro-2,2-dimethylbenzofuran-7-yl]-5-methoxy-1,3,4-oxadiazol-2(3H)-one (compound 2), 9,9-Dimethoxybicyclo[3.3.1]nona-2,4-dione (compound 3), and 3-[3-Bromophenyl]-7-chloro-3,4-dihydro-10-hydroxy-1,9(2H,10H)-acridinedione (compound 4). The insilico investigation revealed that the four tested compounds could be a good candidate to regulate the expression of key genes and may also exert significant cytotoxic effects against several tumor celllines. In addition, these compounds could also be effective in the treatment of some diseases related to diabetes, skin pathologies, cardiovascular, and central nervous system disorders. The bioactive compounds of plant remain the best alternative in the context of the drug discovery and development process.

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Acetylcholinesterase Inhibitors in the Treatment of Neurodegenerative Diseases and the Role of Acetylcholinesterase in their Pathogenesis

Cited by 119 publications

References 539 publications

Medication Rules in Herbal Medicine for Mild Cognitive Impairment: A Network Pharmacology and Data Mining Study

Medication Rules in Herbal Medicine for Mild Cognitive Impairment: A Network Pharmacology and Data Mining Study

Sodium Benzoate—Harmfulness and Potential Use in Therapies for Disorders Related to the Nervous System: A Review

In Silico Investigation of Some Compounds from the N-Butanol Extract of Centaurea tougourensis Boiss. & Reut.

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