scholarly journals Gibbs Free Energy, a Thermodynamic Measure of Protein–Protein Interactions, Correlates with Neurologic Disability

2021 ◽  
Vol 1 (3) ◽  
pp. 201-210
Author(s):  
Michael Keegan ◽  
Hava T. Siegelmann ◽  
Edward A. Rietman ◽  
Giannoula Lakka Klement ◽  
Jack A. Tuszynski
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Free Energy ◽  
Gibbs Free Energy ◽  
Protein Interactions ◽  
Neurological Diseases ◽  
Pearson Correlation ◽  
Brain Network ◽  
Network Organization ◽  
Protein Protein Interactions

Modern network science has been used to reveal new and often fundamental aspects of brain network organization in physiological as well as pathological conditions. As a consequence, these discoveries, which relate to network hierarchy, hubs and network interactions, have begun to change the paradigms of neurodegenerative disorders. In this paper, we explore the use of thermodynamics for protein–protein network interactions in Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS), traumatic brain injury and epilepsy. To assess the validity of using network interactions in neurological diseases, we investigated the relationship between network thermodynamics and molecular systems biology for these neurological disorders. In order to uncover whether there was a correlation between network organization and biological outcomes, we used publicly available RNA transcription data from individual patients with these neurological conditions, and correlated these molecular profiles with their respective individual disability scores. We found a linear correlation (Pearson correlation of −0.828) between disease disability (a clinically validated measurement of a person’s functional status) and Gibbs free energy (a thermodynamic measure of protein–protein interactions). In other words, we found an inverse relationship between disease disability and thermodynamic energy. Because a larger degree of disability correlated with a larger negative drop in Gibbs free energy in a linear disability-dependent fashion, it could be presumed that the progression of neuropathology such as is seen in Alzheimer’s disease could potentially be prevented by therapeutically correcting the changes in Gibbs free energy.

scholarly journals Gibbs Free Energy, a thermodynamic measure of protein-protein interactions, correlates with neurologic disability

2019 ◽  
Author(s):  
Michael Keegan ◽  
Hava T Siegelmann ◽  
Edward A Rietman ◽  
Giannola Lakka Klement
Keyword(s):  
Free Energy ◽  
Alzheimer Disease ◽  
Gibbs Free Energy ◽  
Protein Interactions ◽  
Pearson Correlation ◽  
Brain Network ◽  
Network Organization ◽  
Protein Protein Interactions ◽  
Degree Of Disability ◽  
Neurologic Disability

Background: Modern network science has been used to reveal new and often fundamental aspects of brain network organization in physiological as well as pathological conditions. As a consequence, these discoveries, which relate to network hierarchy, hubs and network interactions, begun to change the paradigms of neurodegenerative disorders. We therefore explored the use of thermodynamics for protein-protein network interactions in Alzheimer disease (AD), Parkinson disease (PD), multiple sclerosis (MS), traumatic brain injury and epilepsy. Methods: To assess the validity of using network interactions in neurological disease, we investigated the relationship between network thermodynamics and molecular systems biology for these neurological disorders. In order to uncover whether there was a correlation between network organization and biological outcomes, we used publicly available RNA transcription data from individual patients with these neurological conditions, and correlated these molecular profiles with their respective individual disability scores. Results: We found a linear correlation (Pearson correlation of -0.828) between disease disability (a clinically validated measurement of a person's functional status), and Gibbs free energy (a thermodynamic measure of protein-protein interactions). In other words, we found an inverse relationship between disease entropy and thermodynamic energy. Interpretation: Because a larger degree of disability correlated with a larger negative drop in Gibbs free energy in a linear, disability-dependent fashion, it could be presumed that the progression of neuropathology such as is seen in Alzheimer Disease, could potentially be prevented by therapeutically correcting the changes Gibbs free energy.

scholarly journals Shared Blood Transcriptomic Signatures between Alzheimer’s Disease and Diabetes Mellitus

Biomedicines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 34
Author(s):  
Taesic Lee ◽  
Hyunju Lee
Keyword(s):  
Diabetes Mellitus ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein Interactions ◽  
Expression Patterns ◽  
Protein Protein Interactions ◽  
Hub Genes ◽  
Gene Modules ◽  
Gene Regulatory ◽  
The Brain

Alzheimer’s disease (AD) and diabetes mellitus (DM) are known to have a shared molecular mechanism. We aimed to identify shared blood transcriptomic signatures between AD and DM. Blood expression datasets for each disease were combined and a co-expression network was used to construct modules consisting of genes with similar expression patterns. For each module, a gene regulatory network based on gene expression and protein-protein interactions was established to identify hub genes. We selected one module, where COPS4, PSMA6, GTF2B, GTF2F2, and SSB were identified as dysregulated transcription factors that were common between AD and DM. These five genes were also differentially co-expressed in disease-related tissues, such as the brain in AD and the pancreas in DM. Our study identified gene modules that were dysregulated in both AD and DM blood samples, which may contribute to reveal common pathophysiology between two diseases.

scholarly journals Thermodynamic measures of cancer: Gibbs free energy and entropy of protein–protein interactions

2016 ◽  
Vol 42 (3) ◽  
pp. 339-350 ◽  
Author(s):  
Edward A. Rietman ◽  
John Platig ◽  
Jack A. Tuszynski ◽  
Giannoula Lakka Klement
Keyword(s):  
Free Energy ◽  
Gibbs Free Energy ◽  
Protein Interactions ◽  
Protein Protein Interactions

P3-308: Functional brain network organization in Alzheimer's disease

2013 ◽  
Vol 9 ◽  
pp. P670-P670 ◽  
Author(s):  
Hanneke de Waal ◽  
Cornelis Stam ◽  
Marieke Lansbergen ◽  
F. Maestú ◽  
Philip Scheltens ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Brain Network ◽  
Network Organization ◽  
Functional Brain ◽  
Functional Brain Network

scholarly journals Alzheimer’s Disease and HLA-A2: Linking Neurodegenerative to Immune Processes through an In Silico Approach

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Ricardo A. Cifuentes ◽  
Juan Murillo-Rojas
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein Interactions ◽  
In Silico ◽  
Meta Analysis ◽  
Specific Antigen ◽  
Case Control ◽  
Interacting Proteins ◽  
Protein Protein Interactions ◽  
Case Control Studies

There is a controversial relationship between HLA-A2 and Alzheimer’s disease (AD). It has been suggested a modifier effect on the risk that depends on genetic loadings. Thus, the aims of this study were to evaluate this relationship and to reveal genes associated with both concepts the HLA-A gene and AD. Consequently, we did first a classical systematic review and a meta-analysis of case-control studies. Next, by means of an in silico approach, we used experimental knowledge of protein-protein interactions to evaluate the top ranked genes shared by both concepts, previously found through text mining. The meta-analysis did not show a significant pooled OR (1.11, 95% CI: 0.98 to 1.24 in Caucasians), in spite of the fact that four of the included studies had a significant OR > 1 and none of them a significant OR < 1. In contrast, the in silico approach retrieved nonrandomly shared genes by both concepts (P= 0.02), which additionally encode truly interacting proteins. The network of proteins encoded byAPP, ICAM-1, ITGB2, ITGAL, SELP, SELL, IL2, IL1B, CD4, andCD8Alinked immune to neurodegenerative processes and highlighted the potential roles in AD pathogenesis of endothelial regulation, infectious diseases, specific antigen presentation, and HLA-A2 in maintaining synapses.

scholarly journals The Positive Side of the Alzheimer’s Disease Amyloid Cross-Interactions: The Case of the Aβ 1-42 Peptide with Tau, TTR, CysC, and ApoA1

Molecules ◽  
2020 ◽  
Vol 25 (10) ◽  
pp. 2439 ◽  
Author(s):  
Lidia Ciccone ◽  
Chenghui Shi ◽  
Davide di Lorenzo ◽  
Anne-Cécile Van Baelen ◽  
Nicolo Tonali
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein Interactions ◽  
Amyloid Β ◽  
Apolipoprotein A1 ◽  
Single Type ◽  
Protein Protein Interactions ◽  
Positive Side ◽  
Amyloid Fibril Formation ◽  
Tau Aggregation

Alzheimer’s disease (AD) represents a progressive amyloidogenic disorder whose advancement is widely recognized to be connected to amyloid-β peptides and Tau aggregation. However, several other processes likely contribute to the development of AD and some of them might be related to protein-protein interactions. Amyloid aggregates usually contain not only single type of amyloid protein, but also other type of proteins and this phenomenon can be rationally explained by the process of protein cross-seeding and co-assembly. Amyloid cross-interaction is ubiquitous in amyloid fibril formation and so a better knowledge of the amyloid interactome could help to further understand the mechanisms of amyloid related diseases. In this review, we discuss about the cross-interactions of amyloid-β peptides, and in particular Aβ1-42, with other amyloids, which have been presented either as integrated part of Aβ neurotoxicity process (such as Tau) or conversely with a preventive role in AD pathogenesis by directly binding to Aβ (such as transthyretin, cystatin C and apolipoprotein A1). Particularly, we will focus on all the possible therapeutic strategies aiming to rescue the Aβ toxicity by taking inspiration from these protein-protein interactions.

Protein-Protein Interactions and Aggregation Inhibitors in Alzheimer’s Disease

2019 ◽  
Vol 19 (7) ◽  
pp. 501-533 ◽  
Author(s):  
Ankit Ganeshpurkar ◽  
Rayala Swetha ◽  
Devendra Kumar ◽  
Gore P. Gangaram ◽  
Ravi Singh ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein Interactions ◽  
Critical Role ◽  
Pdz Domain ◽  
Amyloid Β ◽  
Cellular Prion Protein ◽  
Protein Protein Interactions ◽  
Phosphatase 2A ◽  
Aggregation Inhibitors

Background:Alzheimer’s Disease (AD), a multifaceted disorder, involves complex pathophysiology and plethora of protein-protein interactions. Thus such interactions can be exploited to develop anti-AD drugs.Objective:The interaction of dynamin-related protein 1, cellular prion protein, phosphoprotein phosphatase 2A and Mint 2 with amyloid β, etc., studied recently, may have critical role in progression of the disease. Our objective has been to review such studies and their implications in design and development of drugs against the Alzheimer’s disease.Methods:Such studies have been reviewed and critically assessed.Results:Review has led to show how such studies are useful to develop anti-AD drugs.Conclusion:There are several PPIs which are current topics of research including Drp1, Aβ interactions with various targets including PrPC, Fyn kinase, NMDAR and mGluR5 and interaction of Mint2 with PDZ domain, etc., and thus have potential role in neurodegeneration and AD. Finally, the multi-targeted approach in AD may be fruitful and opens a new vista for identification and targeting of PPIs in various cellular pathways to find a cure for the disease.

scholarly journals Serum Glycoproteomics and Identification of Potential Mechanisms Underlying Alzheimer’s Disease

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Naphatthakarn Kerdsaeng ◽  
Sittiruk Roytrakul ◽  
Suwannee Chanprasertyothin ◽  
Piangporn Charernwat ◽  
Sirintorn Chansirikarnjana ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Signaling Pathway ◽  
Protein Interactions ◽  
Molecular Mechanisms ◽  
Wnt Signaling Pathway ◽  
Cytokine Signaling ◽  
Control Group ◽  
Protein Protein Interactions ◽  
Liquid Chromatography Tandem Mass

Objectives. This study compares glycoproteomes in Thai Alzheimer’s disease (AD) patients with those of cognitively normal individuals. Methods. Study participants included outpatients with clinically diagnosed AD ( N = 136 ) and healthy controls without cognitive impairment ( N = 183 ). Blood samples were collected from all participants for biochemical analysis and for Apolipoprotein   E (APOE) genotyping by real-time TaqMan PCR assays. Comparative serum glycoproteomic profiling by liquid chromatography-tandem mass spectrometry was then performed to identify differentially abundant proteins with functional relevance. Results. Statistical differences in age, educational level, and APOE ɛ3/ɛ4 and ɛ4/ɛ4 haplotype frequencies were found between the AD and control groups. The frequency of the APOE ɛ4 allele was significantly higher in the AD group than in the control group. In total, 871 glycoproteins were identified, including 266 and 259 unique proteins in control and AD groups, respectively. There were 49 and 297 upregulated and downregulated glycoproteins, respectively, in AD samples compared with the controls. Unique AD glycoproteins were associated with numerous pathways, including Alzheimer’s disease-presenilin pathway (16.6%), inflammation pathway mediated by chemokine and cytokine signaling (9.2%), Wnt signaling pathway (8.2%), and apoptosis signaling pathway (6.7%). Conclusion. Functions and pathways associated with protein-protein interactions were identified in AD. Significant changes in these proteins can indicate the molecular mechanisms involved in the pathogenesis of AD, and they have the potential to serve as AD biomarkers. Such findings could allow us to better understand AD pathology.

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