Proximal Pathway Enrichment Analysis for Targeting Comorbid Diseases via Network Endopharmacology

Aguirre‐Plans, Joaquim; Piñero, Janet; Menche, Jörg; Sanz, Ferrán; Furlong, Laura I.; Schmidt, Harald; Oliva, Baldo; Güney, Emre

doi:10.3390/ph11030061

Cited by 37 publications

(26 citation statements)

References 71 publications

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“…Additionally, this study examined genes found in the subject's blood, which may not translate directly to expression within the subject's brain in all cases. Many of the known key players in Alzheimer's disease, such as APP, are differentially expressed between tissue types and between different regions of the brain [48]. With that being said, with further study these genes may prove to be valuable biomarkers for use in much-needed early diagnosis tests, as many of the genes show similar expression patterns and relationships in both MCI and AD individuals and blood is a relatively easily obtained sample.…”

Section: Discussionmentioning

confidence: 99%

Network Medicine Approach for Analysis of Alzheimer’s Disease Gene Expression Data

Cohen

Pilozzi

Huang

2020

IJMS

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Alzheimer’s disease (AD) is the most widespread diagnosed cause of dementia in the elderly. It is a progressive neurodegenerative disease that causes memory loss as well as other detrimental symptoms that are ultimately fatal. Due to the urgent nature of this disease, and the current lack of success in treatment and prevention, it is vital that different methods and approaches are applied to its study in order to better understand its underlying mechanisms. To this end, we have conducted network-based gene co-expression analysis on data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. By processing and filtering gene expression data taken from the blood samples of subjects with varying disease states and constructing networks based on that data to evaluate gene relationships, we have been able to learn about gene expression correlated with the disease, and we have identified several areas of potential research interest.

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Section: Discussionmentioning

confidence: 99%

Network Medicine Approach for Analysis of Alzheimer’s Disease Gene Expression Data

Cohen

Pilozzi

Huang

2020

IJMS

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“…Bioinformatic approaches applied to targets, biomarkers, drug characteristics, and drug-disease pathway proximity will facilitate matching drug processes to disease pathways and assist in developing a robust TS approach. Application of a multiattribute utility theory to develop weighting of TS elements may improve predictability [95, 96].…”

Section: Discussionmentioning

confidence: 99%

Translational Scoring of Candidate Treatments for Alzheimer’s Disease: A Systematic Approach

Cummings

2020

Dement Geriatr Cogn Disord

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Background: There are many failures in treatment development for Alzheimer's disease (AD). Some of these failures are the result of development programs that lacked critical information about candidate drugs as these were advanced from one phase of development to the next. Translational scoring (TS) has been proposed as a means of increasing the rigor with which treatment development programs are executed. Previously, these approaches were not specific to AD or to the phase of drug development. Detailed information on the characteristics needed to advance a candidate agent from one phase to the next is the basis for success in subsequent phases. Summary: The TS approach is presented with a score range of 0-25 for agents entering phases 1, 2, and 3 of development and those that have completed phase 3 and are being considered for regulatory review. Each phase has 5 essential categories scored from 0-5 indicating the completeness of the data available when the agent is being considered for promotion to the next phase. Lower scores suggest that the development program should be reexamined for missing information while higher scores increase the confidence that the agent has the potential to succeed in the next phase. Scoring guidelines are provided and examples of scores for drugs in recent development programs are provided to illustrate the principles of TS. Key Messages: Successful development of drugs for AD treatment requires disciplined informed decision-making at each phase of development. TS is a methodology for more rigorous drug development to help ensure that inadequately characterized drugs are not advanced and that the development platform at each phase is optimal to support success at the next phase.

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“…The drug repurposing candidates that can target common mechanisms involved in T2DM and AD have recently gained attention due to the increased comorbidity among such cases [136]. In the paper of Aguirre-Plans et al [137] authors proposed a novel drug repurposing approach, Proximal pathway Enrichment Analysis"-a powerful computational strategy for targeting multiple pathologies involving common biological pathways in T2DM and AD. 35 of evaluated pathways are shared by both disease entities.…”

Section: Treating Ad With Diabetic Medicationsmentioning

confidence: 99%

The Interplay between Diabetes and Alzheimer’s Disease—In the Hunt for Biomarkers

Kubis-Kubiak

Dyba

Piwowar

2020

IJMS

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The brain is an organ in which energy metabolism occurs most intensively and glucose is an essential and dominant energy substrate. There have been many studies in recent years suggesting a close relationship between type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) as they have many pathophysiological features in common. The condition of hyperglycemia exposes brain cells to the detrimental effects of glucose, increasing protein glycation and is the cause of different non-psychiatric complications. Numerous observational studies show that not only hyperglycemia but also blood glucose levels near lower fasting limits (72 to 99 mg/dL) increase the incidence of AD, regardless of whether T2DM will develop in the future. As the comorbidity of these diseases and earlier development of AD in T2DM sufferers exist, new AD biomarkers are being sought for etiopathogenetic changes associated with early neurodegenerative processes as a result of carbohydrate disorders. The S100B protein seem to be interesting in this respect as it may be a potential candidate, especially important in early diagnostics of these diseases, given that it plays a role in both carbohydrate metabolism disorders and neurodegenerative processes. It is therefore necessary to clarify the relationship between the concentration of the S100B protein and glucose and insulin levels. This paper draws attention to a valuable research objective that may in the future contribute to a better diagnosis of early neurodegenerative changes, in particular in subjects with T2DM and may be a good basis for planning experiments related to this issue as well as a more detailed explanation of the relationship between the neuropathological disturbances and changes of glucose and insulin concentrations in the brain.

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Proximal Pathway Enrichment Analysis for Targeting Comorbid Diseases via Network Endopharmacology

Cited by 37 publications

References 71 publications

Network Medicine Approach for Analysis of Alzheimer’s Disease Gene Expression Data

Network Medicine Approach for Analysis of Alzheimer’s Disease Gene Expression Data

Translational Scoring of Candidate Treatments for Alzheimer’s Disease: A Systematic Approach

The Interplay between Diabetes and Alzheimer’s Disease—In the Hunt for Biomarkers

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