scholarly journals Current and emerging therapeutic targets of alzheimer's disease for the design of multi-target directed ligands

MedChemComm ◽  
2019 ◽  
Vol 10 (12) ◽  
pp. 2052-2072 ◽  
Author(s):  
Laura Blaikie ◽  
Graeme Kay ◽  
Paul Kong Thoo Lin
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Drug Discovery ◽  
Neurodegenerative Disease ◽  
Cause Of Death ◽  
Therapeutic Targets

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease, and a major cause of death worldwide. Since AD is a multi-factorial disease, a MTDL approach to drug discovery is discussed.

DUAL SPECIFICITY PROTEIN PHOSPHATASES: Therapeutic Targets for Cancer and Alzheimer's Disease

2005 ◽  
Vol 45 (1) ◽  
pp. 725-750 ◽  
Author(s):  
Alexander P. Ducruet ◽  
Andreas Vogt ◽  
Peter Wipf ◽  
John S. Lazo
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Drug Discovery ◽  
Therapeutic Targets ◽  
Dual Specificity ◽  
Complete Sequencing ◽  
Dual Specificity Phosphatases ◽  
Molecular Therapeutic ◽  
Specificity Protein ◽  
Molecular Therapeutic Targets

The complete sequencing of the human genome is generating many novel targets for drug discovery. Understanding the pathophysiological roles of these putative targets and assessing their suitability for therapeutic intervention has become the major hurdle for drug discovery efforts. The dual-specificity phosphatases (DSPases), which dephosphorylate serine, threonine, and tyrosine residues in the same protein substrate, have important roles in multiple signaling pathways and appear to be deregulated in cancer and Alzheimer's disease. We examine the potential of DSPases as new molecular therapeutic targets for the treatment of human disease.

scholarly journals Two decades of new drug discovery and development for Alzheimer's disease

RSC Advances ◽  
2017 ◽  
Vol 7 (10) ◽  
pp. 6046-6058 ◽  
Author(s):  
Zhidong Liu ◽  
Aihua Zhang ◽  
Hui Sun ◽  
Ying Han ◽  
Ling Kong ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Drug Discovery ◽  
Cognitive Function ◽  
Neurodegenerative Disease ◽  
Drug Discovery And Development ◽  
New Drug ◽  
Behavioral Abnormalities

Alzheimer's disease is a progressive and irreversible neurodegenerative disease, associated with a decreased cognitive function and severe behavioral abnormalities.

Lighting and Alzheimer’s disease and related dementias: Spotlight on sleep and depression

2021 ◽  
Vol 53 (5) ◽  
pp. 405-422
Author(s):  
MG Figueiro ◽  
HC Kales
Keyword(s):  
Alzheimer’S Disease ◽  
Older Adults ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disease ◽  
Sleep Disturbances ◽  
Well Being ◽  
Pharmacological Intervention ◽  
Negative Effects ◽  
Health And Well Being ◽  
Positive Results

Alzheimer’s disease and related dementias is the collective term for a progressive neurodegenerative disease for which there is presently no cure. This paper focuses on two symptoms of the disease, sleep disturbances and depression, and discusses how light can be used as a non-pharmacological intervention to mitigate their negative effects. Bright days and dark nights are needed for health and well-being, but the present components of the built environment, especially those places where older adults spend most of their days, are too dimly illuminated during the day and too bright at night. To be effective light needs to be correctly specified, implemented and measured. Yet, without the appropriate specification and measurement of the stimulus, researchers will not be able to successfully demonstrate positive results in the field, nor will lighting designers and specifiers have the confidence to implement lighting solutions for promoting better sleep and mood in this population.

scholarly journals Arrayed CRISPR reveals genetic regulators of tau aggregation, autophagy and mitochondria in Alzheimer’s disease model

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lishu Duan ◽  
Mufeng Hu ◽  
Joseph A. Tamm ◽  
Yelena Y. Grinberg ◽  
Fang Shen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Drug Discovery ◽  
Disease Model ◽  
Mitochondrial Morphology ◽  
Individual Gene ◽  
Human Genes ◽  
Future Drug ◽  
Tau Aggregation

AbstractAlzheimer’s disease (AD) is a common neurodegenerative disease with poor prognosis. New options for drug discovery targets are needed. We developed an imaging based arrayed CRISPR method to interrogate the human genome for modulation of in vitro correlates of AD features, and used this to assess 1525 human genes related to tau aggregation, autophagy and mitochondria. This work revealed (I) a network of tau aggregation modulators including the NF-κB pathway and inflammatory signaling, (II) a correlation between mitochondrial morphology, respiratory function and transcriptomics, (III) machine learning predicted novel roles of genes and pathways in autophagic processes and (IV) individual gene function inferences and interactions among biological processes via multi-feature clustering. These studies provide a platform to interrogate underexplored aspects of AD biology and offer several specific hypotheses for future drug discovery efforts.

scholarly journals Artificial intelligence-based computational framework for drug-target prioritization and inference of novel repositionable drugs for Alzheimer’s disease

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Shingo Tsuji ◽  
Takeshi Hase ◽  
Ayako Yachie-Kinoshita ◽  
Taiko Nishino ◽  
Samik Ghosh ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Deep Learning ◽  
Drug Target ◽  
Target Genes ◽  
Drug Repositioning ◽  
Therapeutic Targets ◽  
Machine Learning Techniques ◽  
Computational Framework ◽  
Novel Therapeutic

Abstract Background Identifying novel therapeutic targets is crucial for the successful development of drugs. However, the cost to experimentally identify therapeutic targets is huge and only approximately 400 genes are targets for FDA-approved drugs. As a result, it is inevitable to develop powerful computational tools that can identify potential novel therapeutic targets. Fortunately, the human protein-protein interaction network (PIN) could be a useful resource to achieve this objective. Methods In this study, we developed a deep learning-based computational framework that extracts low-dimensional representations of high-dimensional PIN data. Our computational framework uses latent features and state-of-the-art machine learning techniques to infer potential drug target genes. Results We applied our computational framework to prioritize novel putative target genes for Alzheimer’s disease and successfully identified key genes that may serve as novel therapeutic targets (e.g., DLG4, EGFR, RAC1, SYK, PTK2B, SOCS1). Furthermore, based on these putative targets, we could infer repositionable candidate-compounds for the disease (e.g., tamoxifen, bosutinib, and dasatinib). Conclusions Our deep learning-based computational framework could be a powerful tool to efficiently prioritize new therapeutic targets and enhance the drug repositioning strategy.

scholarly journals Sustainable Drug Discovery of Multi-Target-Directed Ligands for Alzheimer’s Disease

2021 ◽  
Author(s):  
Michele Rossi ◽  
Michela Freschi ◽  
Luciana de Camargo Nascente ◽  
Alessandra Salerno ◽  
Sarah de Melo Viana Teixeira ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Drug Discovery

Challenges in Alzheimer's Disease Drug Discovery and Development: The Role of Modeling, Simulation, and Open Data

2020 ◽  
Vol 107 (4) ◽  
pp. 796-805 ◽  
Author(s):  
Daniela J. Conrado ◽  
Sridhar Duvvuri ◽  
Hugo Geerts ◽  
Jackson Burton ◽  
Carla Biesdorf ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Drug Discovery ◽  
Open Data ◽  
Drug Discovery And Development ◽  
Modeling Simulation

Genetic evidence for microglia-associated pathways as therapeutic targets for Alzheimer's disease

2016 ◽  
Vol 39 ◽  
pp. S6
Author(s):  
Claudio Villegas-Llerena ◽  
Mar Matarin ◽  
John Hardy ◽  
Jennifer Pocock
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Therapeutic Targets ◽  
Genetic Evidence
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