scholarly journals Targeting Cell Signalling Pathways: Novel Targets for Alzheimer’s Disease

2016 ◽  
Vol 1 (3) ◽  
Author(s):  
Mehdi H Shahi
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Signalling ◽  
Signalling Pathways ◽  
Novel Targets

scholarly journals Network Pharmacology-Based Study of the Underlying Mechanisms of Huangqi Sijunzi Decoction for Alzheimer’s Disease

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Wei Zhang ◽  
Mingti Lv ◽  
Yating Shi ◽  
Yonghui Mu ◽  
Zhaoyang Yao ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neuroprotective Effect ◽  
Signalling Pathway ◽  
Signalling Pathways ◽  
Network Pharmacology ◽  
Neuroprotective Effects ◽  
Target Network ◽  
Compound Target

Background. Huangqi Sijunzi decoction (HQSJZD) is a commonly used conventional Chinese herbal medicine prescription for invigorating Qi, tonifying Yang, and removing dampness. Modern pharmacology and clinical applications of HQSJZD have shown that it has a certain curative effect on Alzheimer’s disease (AD). Methods. The active components and targets of HQSJZD were searched in the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The genes corresponding to the targets were retrieved using UniProt and GeneCard database. The herb-compound-target network and protein-protein interaction (PPI) network were constructed by Cytoscape. The core targets of HQSJZD were analysed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The main active compounds of HQSJZD were docked with acetylcholinesterase (AChE). In vitro experiments were conducted to detect the inhibitory and neuroprotective effects of AChE. Results. Compound-target network mainly contained 132 compounds and 255 corresponding targets. The main compounds contained quercetin, kaempferol, formononetin, isorhamnetin, hederagenin, and calycosin. Key targets contained AChE, PTGS2, PPARG, IL-1B, GSK3B, etc. There were 1708 GO items in GO enrichment analysis and 310 signalling pathways in KEGG, mainly including the cAMP signalling pathway, the vascular endothelial growth factor (VEGF) signalling pathway, serotonergic synapses, the calcium signalling pathway, type II diabetes mellitus, arginine and proline metabolism, and the longevity regulating pathway. Molecular docking showed that hederagenin and formononetin were the top 2 compounds of HQSJZD, which had a high affinity with AChE. And formononetin has a good neuroprotective effect, which can improve the oxidative damage of nerve cells. Conclusion. HQSJZD was found to have the potential to treat AD by targeting multiple AD-related targets. Formononetin and hederagenin in HQSJZD may regulate multiple signalling pathways through AChE, which might play a therapeutic role in AD.

Signalling pathways in schistosomes: novel targets for control interventions against schistosomiasis

2017 ◽  
Vol 1 (6) ◽  
pp. 633-639 ◽  
Author(s):  
Pengfei Cai ◽  
Donald P. McManus ◽  
Hong You
Keyword(s):  
Functional Characterization ◽  
Cell Signalling ◽  
Signalling Pathways ◽  
Signal Transduction Pathways ◽  
Future Perspectives ◽  
Self Renewal ◽  
Physiological Processes ◽  
Growth Development ◽  
Novel Targets

Over the last decade, there has been accumulating evidence showing that signalling pathways are involved in extensive biological and physiological processes in the human blood fluke schistosomes, playing essential roles in environmental sensing, host penetration, growth, development, maturation, embryogenesis, tissue self-renewal and survival. Owing to the likelihood of resistance developing against praziquantel, the only drug currently available that is effective against all the human schistosome species, there is an urgent requirement for an alternative treatment, arguing for continuing research into novel or repurposed anti-schistosomal drugs. An increasing number of anticancer drugs are being developed which block abnormal signalling pathways, a feature that has stimulated interest in developing novel interventions against human schistosomiasis by targeting key cell signalling components. In this review, we discuss the functional characterization of signal transduction pathways in schistosomes and consider current challenges and future perspectives in this important area of research.

scholarly journals AD Informer Set: Chemical tools to facilitate Alzheimer's disease drug discovery

2021 ◽  
Author(s):  
Frances M Potjewyd ◽  
Joel K Annor-Gyamfi ◽  
Jeffrey Aube ◽  
Shaoyou Chu ◽  
Ivie L Conlon ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Small Molecules ◽  
Small Molecule ◽  
Positive Control ◽  
Target Validation ◽  
Protein Targets ◽  
Novel Targets ◽  
Chemical Tools ◽  
Small Molecule Modulators

Introduction: The portfolio of novel targets to treat Alzheimer's disease (AD) has been enriched by the AMP-AD program. Methods: A cheminformatics-driven effort enabled identification of existing small molecule modulators for many protein targets nominated by AMP-AD and suitable positive control compounds to be included in the set. Results: We have built an annotated set of 171 small molecule modulators, including mostly inhibitors, targeting 98 unique proteins that have been nominated by AMP-AD consortium members as novel targets for AD treatment. These small molecules vary in their quality and should be considered chemical tools that can be used in efforts to validate therapeutic hypotheses, but which would require further optimization. A physical copy of the AD Informer Set can be ordered via the AD Knowledge Portal. Discussion: Small molecule tools that enable target validation are important tools for the translation of novel hypotheses into viable therapeutic strategies for AD.

scholarly journals STRUCTURAL STUDIES OF ATASE1 AND ATASE2: NOVEL TARGETS FOR ALZHEIMER’S DISEASE AND AGING

2017 ◽  
Vol 1 (suppl_1) ◽  
pp. 253-254
Author(s):  
M.A. Farrugia ◽  
Y. Ding ◽  
M. Feig ◽  
L. Puglielli
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Structural Studies ◽  
Novel Targets

Diabetes as a risk factor for Alzheimer's disease: insulin signalling impairment in the brain as an alternative model of Alzheimer's disease

2011 ◽  
Vol 39 (4) ◽  
pp. 891-897 ◽  
Author(s):  
Christian Hölscher
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Factor ◽  
Growth Factors ◽  
Growth Factor ◽  
Insulin Signalling ◽  
Cell Signalling ◽  
Insulin Receptors ◽  
Model Of Alzheimer’S Disease ◽  
The Brain

Surprisingly little is known about the mechanisms that trigger the onset of AD (Alzheimer's disease) in sporadic forms. A number of risk factors have been identified that may shed light on the mechanisms that may trigger or facilitate the development of AD. Recently, T2DM (Type 2 diabetes mellitus) has been identified as a risk factor for AD. A common observation for both conditions is the desensitization of insulin receptors in the brain. Insulin acts as a growth factor in the brain and is neuroprotective, activates dendritic sprouting, regeneration and stem cell proliferation. The impairment of this important growth factor signal may facilitate the development of AD. Insulin as well as other growth factors have shown neuroprotective properties in preclinical and clinical trials. Several drugs have been developed to treat T2DM, which re-sensitize insulin receptors and may be of use to prevent neurodegenerative processes in the brain. In particular, the incretins GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insolinotropic polypeptide) are hormones that re-sensitize insulin signalling. Incretins also have similar growth-factor-like properties as insulin and are neuroprotective. In mouse models of AD, GLP-1 receptor agonists reduce amyloid plaque formation, reduce the inflammation response in the brain, protect neurons from oxidative stress, induce neurite outgrowth, and protect synaptic plasticity and memory formation from the detrimental effects caused by β-amyloid production and inflammation. Other growth factors such as BDNF (brain-derived neurotrophic factor), NGF (nerve growth factor) or IGF-1 (insulin-like growth factor 1) also have shown a range of neuroprotective properties in preclinical studies. These results show that these growth factors activate similar cell signalling mechanisms that are protective and regenerative, and suggest that the initial process that may trigger the cascade of neurodegenerative events in AD could be the impairment of growth factor signalling such as early insulin receptor desensitization.

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