scholarly journals Recent developments of small molecule γ-secretase modulators for Alzheimer's disease

2020 ◽  
Vol 11 (9) ◽  
pp. 1003-1022 ◽  
Author(s):  
Shekar Mekala ◽  
Grady Nelson ◽  
Yue-Ming Li
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Small Molecule ◽  
Recent Progress ◽  
Review Article ◽  
Gamma Secretase ◽  
Recent Developments

This review article highlights the recent progress and outlook for small molecule gamma secretase modulators for potential Alzheimer's therapies.

P4-294: Gamma-secretase as a target for Alzheimer's disease therapy: Small-molecule development

2013 ◽  
Vol 9 ◽  
pp. P811-P812
Author(s):  
Corinne Augelli-Szafran ◽  
Katherine Brogan ◽  
Cuiman Cai ◽  
Jian Chen ◽  
Yongli Gu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Small Molecule ◽  
Gamma Secretase ◽  
Disease Therapy

scholarly journals Human-Induced Pluripotent Stem Cells and Herbal Small-Molecule Drugs for Treatment of Alzheimer’s Disease

2020 ◽  
Vol 21 (4) ◽  
pp. 1327 ◽  
Author(s):  
Wei Wuli ◽  
Sheng-Tzung Tsai ◽  
Tzyy-Wen Chiou ◽  
Horng-Jyh Harn
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Small Molecule ◽  
Pluripotent Stem Cells ◽  
Gamma Secretase ◽  
Small Molecule Drugs ◽  
Β Amyloid ◽  
Induced Pluripotent

Alzheimer’s disease (AD) is characterized by extracellular amyloid plaques composed of the β-amyloid peptides and intracellular neurofibrillary tangles and associates with progressive declines in memory and cognition. Several genes play important roles and regulate enzymes that produce a pathological accumulation of β-amyloid in the brain, such as gamma secretase (γ-secretase). Induced pluripotent stem cells from patients with Alzheimer’s disease with different underlying genetic mechanisms may help model different phenotypes of Alzheimer’s disease and facilitate personalized drug screening platforms for the identification of small molecules. We also discuss recent developments by γ-secretase inhibitors and modulators in the treatment of AD. In addition, small-molecule drugs isolated from Chinese herbal medicines have been shown effective in treating Alzheimer’s disease. We propose a mechanism of small-molecule drugs in treating Alzheimer’s disease. Combining therapy with different small-molecule drugs may increase the chance of symptomatic treatment. A customized strategy tailored to individuals and in combination with therapy may be a more suitable treatment option for Alzheimer’s disease in the future.

Proteolytic processing of the amyloid-beta protein precursor of Alzheimer's disease

2002 ◽  
Vol 38 ◽  
pp. 37-49 ◽  
Author(s):  
Janelle Nunan ◽  
David H Small
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Beta ◽  
Alternative Pathway ◽  
Protein A ◽  
Proteolytic Processing ◽  
Gamma Secretase ◽  
Amyloid Beta Protein ◽  
Protein Precursor ◽  
Amyloid Beta Protein Precursor

The proteolytic processing of the amyloid-beta protein precursor plays a key role in the development of Alzheimer's disease. Cleavage of the amyloid-beta protein precursor may occur via two pathways, both of which involve the action of proteases called secretases. One pathway, involving beta- and gamma-secretase, liberates amyloid-beta protein, a protein associated with the neurodegeneration seen in Alzheimer's disease. The alternative pathway, involving alpha-secretase, precludes amyloid-beta protein formation. In this review, we describe the progress that has been made in identifying the secretases and their potential as therapeutic targets in the treatment or prevention of Alzheimer's disease.

Identify Compounds' Target Against Alzheimer's Disease Based on In-Silico Approach

2019 ◽  
Vol 16 (3) ◽  
pp. 193-208 ◽  
Author(s):  
Yan Hu ◽  
Guangya Zhou ◽  
Chi Zhang ◽  
Mengying Zhang ◽  
Qin Chen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Small Molecule ◽  
Characteristic Curve ◽  
Machine Learning Algorithms ◽  
Learner Model ◽  
Mao B ◽  
Number Of Patients ◽  
Sar Model ◽  
Set Up

Background: Alzheimer's disease swept every corner of the globe and the number of patients worldwide has been rising. At present, there are as many as 30 million people with Alzheimer's disease in the world, and it is expected to exceed 80 million people by 2050. Consequently, the study of Alzheimer’s drugs has become one of the most popular medical topics. Methods: In this study, in order to build a predicting model for Alzheimer’s drugs and targets, the attribute discriminators CfsSubsetEval, ConsistencySubsetEval and FilteredSubsetEval are combined with search methods such as BestFirst, GeneticSearch and Greedystepwise to filter the molecular descriptors. Then the machine learning algorithms such as BayesNet, SVM, KNN and C4.5 are used to construct the 2D-Structure Activity Relationship(2D-SAR) model. Its modeling results are utilized for Receiver Operating Characteristic curve(ROC) analysis. Results: The prediction rates of correctness using Randomforest for AChE, BChE, MAO-B, BACE1, Tau protein and Non-inhibitor are 77.0%, 79.1%, 100.0%, 94.2%, 93.2% and 94.9%, respectively, which are overwhelming as compared to those of BayesNet, BP, SVM, KNN, AdaBoost and C4.5. Conclusion: In this paper, we conclude that Random Forest is the best learner model for the prediction of Alzheimer’s drugs and targets. Besides, we set up an online server to predict whether a small molecule is the inhibitor of Alzheimer's target at http://47.106.158.30:8080/AD/. Furthermore, it can distinguish the target protein of a small molecule.

scholarly journals “Don’t Phos Over Tau”: recent developments in clinical biomarkers and therapies targeting tau phosphorylation in Alzheimer’s disease and other tauopathies

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Yuxing Xia ◽  
Stefan Prokop ◽  
Benoit I. Giasson
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Kinase Inhibitors ◽  
Tau Phosphorylation ◽  
Phosphorylated Tau ◽  
Clinical Biomarkers ◽  
Early Results ◽  
Recent Developments ◽  
Tau Aggregation

AbstractPhosphorylation is one of the most prevalent post-translational modifications found in aggregated tau isolated from Alzheimer’s disease (AD) patient brains. In tauopathies like AD, increased phosphorylation or hyperphosphorylation can contribute to microtubule dysfunction and is associated with tau aggregation. In this review, we provide an overview of the structure and functions of tau protein as well as the physiologic roles of tau phosphorylation. We also extensively survey tau phosphorylation sites identified in brain tissue and cerebrospinal fluid from AD patients compared to age-matched healthy controls, which may serve as disease-specific biomarkers. Recently, new assays have been developed to measure minute amounts of specific forms of phosphorylated tau in both cerebrospinal fluid and plasma, which could potentially be useful for aiding clinical diagnosis and monitoring disease progression. Additionally, multiple therapies targeting phosphorylated tau are in various stages of clinical trials including kinase inhibitors, phosphatase activators, and tau immunotherapy. With promising early results, therapies that target phosphorylated tau  could be useful at slowing tau hyperphosphorylation and aggregation in AD and other tauopathies.

Sign in / Sign up

Export Citation Format

Share Document