Global differential expression of genes located in the Down Syndrome Critical Region in normal human brain

Montoya, Julio César; Fajardo, Dianora; Peña, Ángela; Sánchez, Adolfo; Domínguez, Martha C.; Satizábal, José María; García-Vallejo, Felipe

doi:10.25100/cm.v45i4.1640

Cited by 13 publications

(10 citation statements)

References 27 publications

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“…Cognitive function such as working memory is involved in insulin signaling dysfunction and blood glucose levels. It was reported that working memory is linked with T2MD [35][36][37].…”

Section: Shared Crebbp Mapk and Pi3k-akt Pathways Between Ad And T2dmmentioning

confidence: 99%

Shared Causal Paths underlying Alzheimer’s dementia and Type 2 Diabetes

Jiao

Wang

et al. 2020

Sci Rep

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Background: Although Alzheimer's disease (AD) is a central nervous system disease and type 2 diabetes mellitus (T2DM) is a metabolic disorder, an increasing number of genetic epidemiological studies show clear link between AD and T2DM. The current approach to uncovering the shared pathways between AD and T2DM involves association analysis; however, such analyses lack power to discover the mechanisms of the diseases. Methods:We develop novel statistical methods to shift the current paradigm of genetic analysis from association analysis to deep causal inference for uncovering the shared mechanisms between AD and T2DM, and develop pipelines to infer multilevel omics causal networks which lead to shifting the current paradigm of genetic analysis from genetic analysis alone to integrated causal genomic, epigenomic, transcriptional and phenotypic data analysis. To discover common causal paths from genetic variants to AD and T2DM, we also develop algorithms that can automatically search the causal paths from genetic variants to diseases and Results: The proposed methods and algorithms are applied to ROSMAP dataset with 432 individuals who simultaneously had genotype, RNA-seq, DNA methylation and some phenotypes. We construct multi-omics causal networks and identify 13 shared causal genes, 16 shared causal pathways between AD and T2DM, and 754 gene expression and 101 gene methylation nodes that were connected to both AD and T2DM in multi-omics causal networks. Conclusions:The results of application of the proposed pipelines for identifying causal paths to real data analysis of AD and T2DM provided strong evidence to support the link between AD and T2DM and unraveled causal mechanism to explain this link.

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“…Cognitive function such as working memory is involved in insulin signaling dysfunction and blood glucose levels. It was reported that working memory is linked with T2MD [35][36][37].…”

Section: Shared Crebbp Mapk and Pi3k-akt Pathways Between Ad And T2dmmentioning

confidence: 99%

Shared Causal Paths underlying Alzheimer’s dementia and Type 2 Diabetes

Jiao

Wang

et al. 2020

Sci Rep

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“…One of them, SOD1 (superoxide dismutase 1), is responsible for maintaining the oxidative balance. The overexpression of SOD1 leads to an imbalance between oxidative factors and antioxidants, which contributes to neuroinflammation and increased Aβ production [112]. Also, the recent studies have shown that polymorphism of β-secretase (BACE-1) has a significant influence on the development of familial AD [113][114][115].…”

Section: Alzheimer's Disease As a Consequence Of Other Diseasesmentioning

confidence: 99%

“…Disruption of mitochondrial processes, especially the mitochondrial respiratory chain, stimulates the production of ROS, which promotes the pathogenesis of AD and neuronal apoptosis. Mitochondrial dysfunction is believed to be directly responsible for cognitive decline because the resulting energy deficits disrupt cholinergic neurotransmission [98,99,112,[116][117][118][119]. Two cohort studies of AD in DS patients are currently recruiting participants (NCT04149197, NCT03901261), and this may shed light on the development of dementia in DS patients.…”

Section: Alzheimer's Disease As a Consequence Of Other Diseasesmentioning

confidence: 99%

A review of the mechanisms underlying selected comorbidities in Alzheimer’s disease

2021

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Alzheimer's disease (AD) is a progressive neurodegenerative disorder of the central nervous system (CNS) leading to mental deterioration and devastation, and eventually a fatal outcome. AD affects mostly the elderly. AD is frequently accompanied by hypercholesterolemia, hypertension, atherosclerosis, and diabetes mellitus, and these are significant risk factors of AD. Other conditions triggered by the progression of AD include psychosis, sleep disorders, epilepsy, and depression. One important comorbidity is Down’s syndrome, which directly contributes to the severity and rapid progression of AD. The development of new therapeutic strategies for AD includes the repurposing of drugs currently used for the treatment of comorbidities. A better understanding of the influence of comorbidities on the pathogenesis of AD, and the medications used in its treatment, might allow better control of disease progression, and more effective pharmacotherapy. Graphic abstract

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“…This terabyte amount data of information is necessary to be analyzed by computational simulation procedures that use bioinformatics analysis tools to get information about the spatial and temporal gene expression. Moreover, the bioinformatics analysis permits to extract information about genes which are expressed in normal and pathological samples of postmortem brains [34,35].…”

Section: As Shown Inmentioning

confidence: 99%

Functional Neurogenomics: A New Approach to Study Cognitive Disability in Down Syndrome Brain

García-Vallejo¹,

Ortiz²,

Gómez³

et al. 2018

Advances in Research on Down Syndrome

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Functional neurogenomics is the interface between neurosciences knowledge and Omics sciences data. It characterizes, identifies, and analyzes expression of genes involved in the function of several structures of brain and cognition. Its major goal is to understand the main pathways of brain function, plasticity, and the etiopathogenesis of brain diseases. We have done an integrate analysis of global brain gene expression linked to cognitive disability in Down syndrome. It is a new approach to better understand the control of complex brain networks of gene expression involved in this syndrome. The objective of the chapter is to present computationally simulate data of global expression of 108 genes associated with cognitive disability and neuroplasticity from DNA microarray experiments of postmortem brain from normal controls and patients with Down syndrome. Some genes that were studied are involved in metabolic process and also promote hippocampal plasticity; interventions reawaken the neural plasticity may permit improved cognition. One of the striking findings was that some of the causes of dysregulation appear to result in the brain being trapped in an immature state of synaptic development. Understanding the functional neurogenomics of Down syndrome brain, emerge a new scenario to partially overcome cognitive disability through new prospective genomic therapies.

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Global differential expression of genes located in the Down Syndrome Critical Region in normal human brain

Cited by 13 publications

References 27 publications

Shared Causal Paths underlying Alzheimer’s dementia and Type 2 Diabetes

Shared Causal Paths underlying Alzheimer’s dementia and Type 2 Diabetes

A review of the mechanisms underlying selected comorbidities in Alzheimer’s disease

Functional Neurogenomics: A New Approach to Study Cognitive Disability in Down Syndrome Brain

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