Dissecting genetic links between Alzheimer’s disease and type 2 diabetes mellitus in a systems biology way

Kang, Peiyuan; Wang, Zhao; Qiao, Dan; Zhang, Bohan; Mu, Chen-Yu; Cui, Huixian; Li, Sha

doi:10.3389/fgene.2022.1019860

Cited by 7 publications

(6 citation statements)

References 29 publications

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“… Afzal et al (2023) uncovered the mutual genomics motifs between AD and T2D via non-negative matrix factorization, and screened of six shared genes. Kang et al (2022) constructed a PPI network consisting of AD and T2DM DEGs and found that the hub gene SLC2A2 (coding transmembrane carrier protein GLUT2), which connects the most DEGs in both AD and T2DM, plays a key regulator in linking T2DM and AD via glucose metabolism-related pathways. Shu et al (2022) identified Five hub proteins between AD and T2D.…”

Section: Identification Of Shared Candidate Biomarkers Between Ad And...mentioning

confidence: 99%

A review and analysis of key biomarkers in Alzheimer’s disease

Zhang,

Liu,

Zhang

et al. 2024

Front. Neurosci.

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Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that affects over 50 million elderly individuals worldwide. Although the pathogenesis of AD is not fully understood, based on current research, researchers are able to identify potential biomarker genes and proteins that may serve as effective targets against AD. This article aims to present a comprehensive overview of recent advances in AD biomarker identification, with highlights on the use of various algorithms, the exploration of relevant biological processes, and the investigation of shared biomarkers with co-occurring diseases. Additionally, this article includes a statistical analysis of key genes reported in the research literature, and identifies the intersection with AD-related gene sets from databases such as AlzGen, GeneCard, and DisGeNet. For these gene sets, besides enrichment analysis, protein–protein interaction (PPI) networks utilized to identify central genes among the overlapping genes. Enrichment analysis, protein interaction network analysis, and tissue-specific connectedness analysis based on GTEx database performed on multiple groups of overlapping genes. Our work has laid the foundation for a better understanding of the molecular mechanisms of AD and more accurate identification of key AD markers.

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Section: Identification Of Shared Candidate Biomarkers Between Ad And...mentioning

confidence: 99%

A review and analysis of key biomarkers in Alzheimer’s disease

Zhang,

Liu,

Zhang

et al. 2024

Front. Neurosci.

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“…Recently, to understand the genetic link between type 2 diabetes and AD, a study was performed to recognize the overlapping gene signatures. SLC2A2 was identified as the crosstalk gene possibly linking these two diseases 36 . Further, Hao and his colleagues carried out a genome-wide association study.…”

Section: Role Of Ros In Diabetes-induced Dementiamentioning

confidence: 99%

Targeting redox imbalance in neurodegeneration: characterizing the role of GLP-1 receptor agonists

Ghosh,

Fontanella,

Scisciola

et al. 2023

Theranostics

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Reactive oxygen species (ROS) have emerged as essential signaling molecules regulating cell survival, death, inflammation, differentiation, growth, and immune response. Environmental factors, genetic factors, or many pathological condition such as diabetes increase the level of ROS generation by elevating the production of advanced glycation end products, reducing free radical scavengers, increasing mitochondrial oxidative stress, and by interfering with DAG-PKC-NADPH oxidase and xanthine oxidase pathways. Oxidative stress, and therefore the accumulation of intracellular ROS, determines the deregulation of several proteins and caspases, damages DNA and RNA, and interferes with normal neuronal function. Furthermore, ROS play an essential role in the polymerization, phosphorylation, and aggregation of tau and amyloid-beta, key mediators of cognitive function decline. At the neuronal level, ROS interfere with the DNA methylation pattern and various apoptotic factors related to cell death, promoting neurodegeneration. Only few drugs are able to quench ROS production in neurons. The cross-linking pathways between diabetes and dementia suggest that antidiabetic medications can potentially treat dementia. Among antidiabetic drugs, glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been found to reduce ROS generation and ameliorate mitochondrial function, protein aggregation, neuroinflammation, synaptic plasticity, learning, and memory. The incretin hormone glucagon-like peptide-1 (GLP-1) is produced by the enteroendocrine L cells in the distal intestine after food ingestion. Upon interacting with its receptor (GLP-1R), it regulates blood glucose levels by inducing insulin secretion, inhibiting glucagon production, and slowing gastric emptying. No study has evidenced a specific GLP-1RA pathway that quenches ROS production. Here we summarize the effects of GLP-1RAs against ROS overproduction and discuss the putative efficacy of Exendin-4, Lixisenatide, and Liraglutide in treating dementia by decreasing ROS.

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“…One of them associates the development of AD to type 2 diabetes mellitus (T2DM), in which the link between these two conditions is protein kinase AMPK, where the progression of T2DM can lead to cognitive impairment . Furthermore, there is a possibility that T2DM may affect the development of AD through insulin signaling in the brain …”

Section: Introductionmentioning

confidence: 99%

“…9 Furthermore, there is a possibility that T2DM may affect the development of AD through insulin signaling in the brain. 10 5′ AMP-activated protein kinase (AMPK) is a metabolic enzyme that plays important roles in both AD and T2DM. 9 Studies have shown that this enzyme can increase glucose transport and regulate free fatty acids in T2DM.…”

Section: Introductionmentioning

confidence: 99%

Molecular Dynamics-Assisted Interaction of Vanadium Complex–AMPK: From Force Field Development to Biological Application for Alzheimer’s Treatment

et al. 2023

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A large part of the world’s population is affected by Alzheimer’s disease (AD) and diabetes mellitus type 2, which cause both social and economic impacts. These two conditions are associated with one protein, AMPK. Studies have shown that vanadium complexes, such as bis(N′,N′-dimethylbiguanidato)-oxovanadium(IV), VO(metf)2·H2O, are potential agents against AD. A crucial step in drug design studies is obtaining information about the structure and interaction of these complexes with the biological targets involved in the process through molecular dynamics (MD) simulations. However, MD simulations depend on the choice of a good force field that could present reliable results. Moreover, general force fields are not efficient for describing the properties of metal complexes, and a VO(metf)2·H2O-specific force field does not yet exist; thus, the proper development of a parameter set is necessary. Furthermore, this investigation is essential and relevant given the importance for both the scientific community and the population that is affected by this neurodegenerative disease. Therefore, the present work aims to develop and validate the AMBER force field parameters for VO(metf)2·H2O since the literature lacks such information on metal complexes and investigate through classical molecular dynamics the interactions made by the complex with the protein. The proposed force field proved to be effective for describing the vanadium complex (VC), supported by different analyses and validations. Moreover, it had a great performance when compared to the general AMBER force field. Beyond that, MD findings provided an in-depth perspective of vanadium complex–protein interactions that should be taken into consideration in future studies.

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Dissecting genetic links between Alzheimer’s disease and type 2 diabetes mellitus in a systems biology way

Cited by 7 publications

References 29 publications

A review and analysis of key biomarkers in Alzheimer’s disease

A review and analysis of key biomarkers in Alzheimer’s disease

Targeting redox imbalance in neurodegeneration: characterizing the role of GLP-1 receptor agonists

Molecular Dynamics-Assisted Interaction of Vanadium Complex–AMPK: From Force Field Development to Biological Application for Alzheimer’s Treatment

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