scholarly journals MAP/Microtubule Affinity Regulating Kinase 4 Inhibitory Potential of Irisin: A New Therapeutic Strategy to Combat Cancer and Alzheimer’s Disease

2021 ◽  
Vol 22 (20) ◽  
pp. 10986
Author(s):  
Rashid Waseem ◽  
Saleha Anwar ◽  
Shama Khan ◽  
Anas Shamsi ◽  
Md. Imtaiyaz Hassan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Therapeutic Strategy ◽  
Disease Therapy ◽  
Cancer Types ◽  
Critical Residues ◽  
Clinically Significant ◽  
Inhibitory Potential ◽  
Valuable Role

Irisin is a clinically significant protein playing a valuable role in regulating various diseases. Irisin attenuates synaptic and memory dysfunction, highlighting its importance in Alzheimer’s disease. On the other hand, Microtubule Affinity Regulating Kinase 4 (MARK4) is associated with various cancer types, uncontrolled neuronal migrations, and disrupted microtubule dynamics. In addition, MARK4 has been explored as a potential drug target for cancer and Alzheimer’s disease therapy. Here, we studied the binding and subsequent inhibition of MARK4 by irisin. Irisin binds to MARK4 with an admirable affinity (K = 0.8 × 107 M−1), subsequently inhibiting its activity (IC50 = 2.71 µm). In vitro studies were further validated by docking and simulations. Molecular docking revealed several hydrogen bonds between irisin and MARK4, including critical residues, Lys38, Val40, and Ser134. Furthermore, the molecular dynamic simulation showed that the binding of irisin resulted in enhanced stability of MARK4. This study provides a rationale to use irisin as a therapeutic agent to treat MARK4-associated diseases.

Drug Design of Inhibitors of Alzheimer’s Disease (AD): POM and DFT Analyses of Cholinesterase Inhibitory Activity of β-amino di-Carbonyl Derivatives

2019 ◽  
Vol 19 (8) ◽  
pp. 688-705
Author(s):  
Taibi Ben Hadda ◽  
Abdur Rauf ◽  
Hsaine Zgou ◽  
Fatma Sezer Senol ◽  
Ilkay Erdogan Orhan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cholinesterase Inhibitors ◽  
Metal Accumulation ◽  
Microtiter Plate ◽  
Metal Chelation ◽  
Carbonyl Derivatives ◽  
Cholinesterase Inhibitory Activity ◽  
Inhibitory Potential

Background:Since deficit of acetylcholine has been evidenced in the Alzheimer’s disease (AD) patients, cholinesterase inhibitors are currently the most specified drug category for the remediation of AD.Method:In the present study, 16 compounds (1-16) with dicarbonyl skeletons have been synthesized and tested for their inhibitory potential in vitro against AChE and BChE using ELISA microtiter plate assays at 100 μg/mL. Since metal accumulation is related to AD, the compounds were also tested for their metal-chelation capacity.Results and Conclusion:All the investigated dicarbonyl compounds exerted none or lower than 30% inhibition against both cholinesterases, whereas compounds 2, 8 and 11 showed 37, 42, 41% of inhibition towards BChE, being the most active. The highest metal-chelation capacity was observed with compound 8 (53.58 ± 2.06%). POM and DFT analyses are in good harmonization with experimental data.

scholarly journals The Therapeutic Potential of Berberis darwinii Stem-Bark: Quantification of Berberine and In Vitro Evidence for Alzheimer's Disease Therapy

2011 ◽  
Vol 6 (8) ◽  
pp. 1934578X1100600 ◽  
Author(s):  
Solomon Habtemariam
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Charles Darwin ◽  
Potent Inhibitor ◽  
Methanolic Extract ◽  
Therapeutic Potential ◽  
Stem Bark ◽  
Acetylcholinesterase Inhibition ◽  
Disease Therapy

Berberis darwinii is native to South America but has been widely distributed in Europe and other continents following its discovery by Charles Darwin. Herewith, the therapeutic potential of stem-bark of the plant for treating Alzheimer's disease was studied using an in vitro acetylcholinesterase inhibition assay. It was found that the methanolic extract of the stem-bark was a potent inhibitor of the enzyme with an IC50 value of 1.23 ± 0.05 μg/mL. An HPLC-based berberine quantification study revealed an astonishing 38% yield of the dried methanolic extract.

scholarly journals Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy

Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 350
Author(s):  
Ashwani Arya ◽  
Rubal Chahal ◽  
Rekha Rao ◽  
Md. Habibur Rahman ◽  
Deepak Kaushik ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Biological Activities ◽  
Structural Diversity ◽  
Time Frame ◽  
World Health ◽  
Cholinergic Transmission ◽  
Disease Therapy ◽  
Inhibitory Potential ◽  
Health Organization

Alzheimer’s disease (AD) is a gradually growing irreversible illness of the brain that almost affects every fifth person (aged > 80 years) in the world. World Health Organization (WHO) also revealed that the prevalence of this disease will enhance (upto double) significantly upto 2030. The poor cholinergic transmission at the synapse is considered to be one of the main reasons behind the progression and occurrence of this disorder. Natural inhibitors of acetylcholine (ACh) such as galanthamine and rivastigmine are used commercially in the treatmentof AD. The biomolecules such assesquiterpenes, possess a great structural diversity and are responsible for a plethora of pharmacological properties. The potential of various sesquiterpenes as anticholinesterase has been reviewed in this article. For this purpose, the various databases, mainly PubMed, Scopus, and Web of Science were investigatedwith different keywords such as “sesquiterpenes+acetylcholinesterase” and “sesquiterpenes+cholinesterase+inhibitors” in the surveyed time frame (2010–2020). A vast literature was evident in the last decade, which affirms the potential of various sesquiterpenes in the improvement of cholinergic transmission by inhibiting the AChE. After data analysis, it was found that 12 compounds out of a total of 58 sesquiterpenes were reported to possess IC50 < 9μM and can be considered as potential candidates for the improvement of learning and memory. Sesquiterpene is an important category of terpenoids, found to possess a large spectrum of biological activities. The outcome of the review clearly states that sesquiterpenes (such as amberboin, lipidiol,etc) from herbs could offer fresh, functional compounds for possible prevention and treatment of AD.

Oral Brain-Targeted Microemulsion for Enhanced Piperine Delivery in Alzheimer’s Disease Therapy: In Vitro Appraisal, In Vivo Activity, and Nanotoxicity

2018 ◽  
Vol 19 (8) ◽  
pp. 3698-3711 ◽  
Author(s):  
Samar M. Etman ◽  
Yosra S. R. Elnaggar ◽  
Doaa A. Abdelmonsif ◽  
Ossama Y. Abdallah
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Therapy

P1-237: Extracorporeal Aβ removal system (EARS) for Alzheimer's disease therapy: Novel devices with fragments of hollow fibers removed Aβ effectively both in vitro and in vivo

2012 ◽  
Vol 8 (4S_Part_5) ◽  
pp. P189-P190
Author(s):  
Nobuya Kitaguchi ◽  
Takehiro Gotoh ◽  
Kazunori Kawaguchi ◽  
Hideo Hori ◽  
Atsushi Ohashi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Hollow Fibers ◽  
Disease Therapy ◽  
Novel Devices ◽  
Removal System

scholarly journals Photoactivation of TGFβ/SMAD signaling pathway ameliorates adult hippocampal neurogenesis in Alzheimer’s disease model

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Xiaolei Wu ◽  
Qi Shen ◽  
Zhan Zhang ◽  
Di Zhang ◽  
Ying Gu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Signaling Pathway ◽  
Therapeutic Strategy ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Smad Signaling ◽  
Smad Signaling Pathway ◽  
Newborn Neurons

Abstract Background Adult hippocampal neurogenesis (AHN) is restricted under the pathological conditions of neurodegenerative diseases, especially in Alzheimer’s disease (AD). The drop of AHN reduces neural circuit plasticity, resulting in the decrease of the generation of newborn neurons in dentate gyrus (DG), which makes it difficult to recover from learning/memory dysfunction in AD, therefore, it is imperative to find a therapeutic strategy to promote neurogenesis and clarify its underlying mechanism involved. Methods Amyloid precursor protein/presenilin 1 (APP/PS1) mice were treated with photobiomodulation therapy (PBMT) for 0.1 mW/mm2 per day in the dark for 1 month (10 min for each day). The neural stem cells (NSCs) were isolated from hippocampus of APP/PS1 transgenic mice at E14, and the cells were treated with PBMT for 0.667 mW/mm2 in the dark (5 min for each time). Results In this study, photobiomodulation therapy (PBMT) is found to promote AHN in APP/PS1 mice. The latent transforming growth factor-β1 (LTGFβ1) was activated in vitro and in vivo during PBMT-induced AHN, which promoted the differentiation of hippocampal APP/PS1 NSCs into newborn neurons. In particular, behavioral experiments showed that PBMT enhanced the spatial learning/memory ability of APP/PS1 mice. Mechanistically, PBMT-stimulated reactive oxygen species (ROS) activates TGFβ/Smad signaling pathway to increase the interaction of the transcription factors Smad2/3 with Smad4 and competitively reduce the association of Smad1/5/9 with Smad4, thereby significantly upregulating the expression of doublecortin (Dcx)/neuronal class-III β-tubulin (Tuj1) and downregulating the expression of glial fibrillary acidic protein (GFAP). These in vitro effects were abrogated when eliminating ROS. Furthermore, specific inhibition of TGFβ receptor I (TGFβR I) attenuates the DNA-binding efficiency of Smad2/3 to the Dcx promotor triggered by PBMT. Conclusion Our study demonstrates that PBMT, as a viable therapeutic strategy, directs the adult hippocampal APP/PS1 NSCs differentiate towards neurons, which has great potential value for ameliorating the drop of AHN in Alzheimer’s disease mice.

Cannabis Sativa L. Flower and Bud Extracts inhibited In vitro Cholinesterases and b-Secretase Enzymes Activities: Possible Mechanisms of Cannabis use in Alzheimer Disease

2021 ◽  
Vol 21 ◽  
Author(s):  
Teboho Mooko ◽  
Asis Bala ◽  
Satyajit Tripathy ◽  
Chethan S. Kumar ◽  
Chandrashekara P. Mahadevappa ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Enzyme Activity ◽  
High Performance ◽  
Cannabis Sativa ◽  
Vero Cells ◽  
Scientific Data ◽  
Secretase Activity ◽  
Inhibitory Potential

Background: There are anecdotal claims on the use of Cannabis sativa L. in the treatment of Alzheimer’s disease, but there is lack of scientific data to support the efficacy and safety of Cannabis sativa L. for Alzheimer’s disease. Aim: The aim of the study was to evaluate the effect of aerial parts of Cannabis sativa L. on the cholinesterases and β-secretase enzyme activity as one of the possible mechanisms of Alzheimer’s disease. Methods: The phytochemical and heavy metal contents were analysed. The extracts were screened for acetylcholinesterase, butyrylcholinesterase and β-secretase activity. Cytotoxicity of extracts was performed in normal vero and pre-adipocytes cell lines. The extracts were characterized using high performance thin layer chromatography and high-performance liquid chromatography for their chemical fingerprints. Alkaloids, flavonoids and glycosides were present amongst the tested phytochemicals. Cannabidiol concentrations were comparatively high in the hexane and dichloromethane than in dichloromethane: methanol (1:1) and methanol extracts. Results: Hexane and dichloromethane extracts showed a better inhibitory potential towards cholinesterase activity, while water, hexane, dichloromethane: methanol (1:1) and methanol showed an inhibitory potential towards β-secretase enzyme activity. All extracts showed no cytotoxic effect on pre-adipocytes and vero cells after 24- and 48-hours of exposure. Conclusion: Therefore, this may explain the mechanism through which AD symptoms may be treated and managed by Cannabis sativa L. extracts.

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