Fast High-Throughput Screening of Alzheimer's Disease by Direct Apolipoprotein E Genotyping-based Multichannel Microchip Electrophoresis

2017 ◽  
Vol 38 (8) ◽  
pp. 948-951
Author(s):  
Yucheng Sun ◽  
Nain Woo ◽  
Su-Kang Kim ◽  
Seong Ho Kang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Apolipoprotein E ◽  
High Throughput ◽  
High Throughput Screening ◽  
Microchip Electrophoresis

[P3-245]: ANALYSIS OF THE HUMORAL RESPONSE IN ALZHEIMER's DISEASE USING THE HIGH-THROUGHPUT SCREENING COMBINATION OF T7 PHAGE LIBRARIES AND PROTEIN MICROARRAYS

2017 ◽  
Vol 13 (7S_Part_21) ◽  
pp. P1034-P1034
Author(s):  
Pablo San Segundo-Acosta ◽  
Ana Montero-Calle ◽  
Maria Garranzo-Asensio ◽  
Carmen Oeo-Santos ◽  
Juan Carlos López-Rodríguez ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
High Throughput ◽  
High Throughput Screening ◽  
Humoral Response ◽  
Protein Microarrays ◽  
Phage Libraries ◽  
T7 Phage

An integrated strategy for rapid screening of multi-target lead compounds for the treatment of Alzheimer's disease from traditional Chinese medicines by UHPLC combined with high-throughput screening: A case study on Salviae Miltiorrhizae Radix et Rhizoma

2021 ◽  
Vol 17 ◽  
Author(s):  
Minmin Zhang ◽  
Siduo Zhou ◽  
Wei Liu ◽  
Huijiao Yan ◽  
Xiao Wang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
High Throughput ◽  
Inhibitory Activity ◽  
High Throughput Screening ◽  
Hplc Analysis ◽  
Salviae Miltiorrhizae ◽  
Salviae Miltiorrhizae Radix ◽  
Ache Inhibitory Activity

Background: Salviae Miltiorrhizae Radix et Rhizoma (Red Sage root) is widely used in traditional Chinese medicine (TCM) for the treatment of Alzheimer’s disease (AD) with demonstrated curative effects, based on the concept of "one drug with multiple therapeutic targets," which appears to be a good strategy for AD treatment. Objective: This study aimed to develop of high-throughput screening (HTS) method for multi-therapeutic target components found in complex TCMs, which are active against AD, using Red Sage root as the case study. Method: Acetylcholinesterase (AChE) inhibitors (AChEIs) from Red Sage root extracts were pre-screened by ultrafiltration-HPLC (UF-HPLC) analysis, in which AChE was added to the extract and then ultrafiltered to remove non-binding compounds. Potential AChEIs were identified by HPLC analysis of compounds bound to AChE. A microplate-based HTS was then used to quantify the AChE inhibitory activity and antioxidant activity of the pre-screened compounds. Results: Pre-screening found ten potential inhibitors, which were identified by ESI-TOF/MS; six of these were purified by semi-preparative HPLC: Oleoyl neocryptotanshinone (1), Dihydrotanshinone Ⅰ (2), Cryptotanshinone (3), Tanshinone Ⅰ (4), Tanshinone ⅡA (5) and Miltirone (6). All six compounds had good AChE inhibitory activity and weak DPPH scavenging capacity. Conclusion: This study provides a platform and technology support for the rapid discovery of multi-target components, potentially active against AD, from complex TCMs and with strong potential for adaptation to the discovery of treatments for other diseases.

scholarly journals High Throughput Screening at the Membrane Interface Reveals New Inhibitors of Amyloid-β

2019 ◽  
Author(s):  
Sarah J. Cox ◽  
Brian Lam ◽  
Ajay Prasad ◽  
Hannah A. Marietta ◽  
Nicholas V. Stander ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Membrane ◽  
Small Molecules ◽  
High Throughput ◽  
High Throughput Screening ◽  
Amyloid Β ◽  
Amyloid Aggregation ◽  
Membrane Interface

Amyloid-β aggregation at the cell-membrane of neruonal cells is implicated as a source of toxicity for Alzheimer’s disease. Small molecules have been studied for their ability to supress amyloid aggregation and toxicity, but the presence of membranes negate their activity. Here, we have identified 5 small molecules that are active at the membrane interface.

scholarly journals High-Throughput Screening and Molecular Dynamics Simulation of Natural Product-like Compounds against Alzheimer’s Disease through Multitarget Approach

2021 ◽  
Vol 14 (9) ◽  
pp. 937
Author(s):  
Danish Iqbal ◽  
Md Tabish Rehman ◽  
Abdulaziz Bin Dukhyil ◽  
Syed Mohd Danish Rizvi ◽  
Mohamed F. Al Ajmi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
Natural Product ◽  
High Throughput ◽  
High Throughput Screening ◽  
Dynamics Simulation ◽  
Potential Candidate ◽  
Stable Conformation

Alzheimer’s disease (AD) is a progressive neurological disorder that affects 50 million people. Despite this, only two classes of medication have been approved by the FDA. Therefore, we have planned to develop therapeutics by multitarget approach. We have explored the library of 2029 natural product-like compounds for their multi-targeting potential against AD by inhibiting AChE, BChE (cholinergic pathway) MAO-A, and MOA-B (oxidative stress pathway) through in silico high-throughput screening and molecular dynamics simulation. Based on the binding energy of these target enzymes, approximately 189 compounds exhibited a score of less than −10 kcal/mol against all targets. However, none of the control inhibitors exhibited a binding affinity of less than −10 kcal/mol. Among these, the top 10 hits of compounds against all four targets were selected for ADME-T analysis. As a result, only F0850-4777 exhibited an acceptable range of physicochemical properties, drug-likeness, pharmacokinetics, and suitability for BBB permeation with high GI-A and non-toxic effects. The molecular dynamics study confirmed that F0850-4777 remained inside the binding cavity of targets in a stable conformation throughout the simulation and Prime-MM/GBSA study revealed that van der Waals’ energy (ΔGvdW) and non-polar solvation or lipophilic energy (ΔGSol_Lipo) contribute favorably towards the formation of a stable protein–ligand complex. Thus, F0850-4777 could be a potential candidate against multiple targets of two pathophysiological pathways of AD and opens the doors for further confirmation through in vitro and in vivo systems.

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