Complex Network-Driven View of Genomic Mechanisms Underlying Parkinson’s Disease: Analyses in Dorsal Motor Vagal Nucleus, Locus Coeruleus, and Substantia Nigra

Corradini, Beatriz Raposo; Iamashita, Priscila; Tampellini, Edilaine; Farfel, José Marcelo; Grinberg, Lea T.; Moreira-Filho, Carlos Alberto

doi:10.1155/2014/543673

Cited by 33 publications

(38 citation statements)

References 125 publications

(150 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We first combined two large microarray expression datasets for three neurodegenerative disorders: AD and HD with their respective controls (Narayanan et al, 2014), and PD with its respective controls (Corradini et al, 2014) (Figure 1). These gene expression data were either taken from human post-mortem prefrontal cortex (AD + HD), or human post-mortem substantia nigra (PD).…”

Section: Resultsmentioning

confidence: 99%

“…For analysis of aging and disease, datasets from studies with multiple time points across age for control and neurodegenerative disease brains were selected. Human AD, HD, and PD disease studies that met these selection criteria, GSE33000 [microarray, prefrontal cortex, brain (Narayanan et al, 2014)] and GSE43490 [microarray, substantia nigra, brain (Corradini et al, 2014)] were analyzed. For cross species comparison, mouse hippocampus RNA-seq datasets from studies with multiple time points across age were selected: GSE61915 (Stilling et al, 2014), GSE73503 (Aaronson and Rosinski, 2015) and GSE83931 (Bundy et al, 2017).…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

A Microglial Signature Directing Human Aging and Neurodegeneration-Related Gene Networks

et al. 2019

View full text Add to dashboard Cite

Aging is regarded as a major risk factor for neurodegenerative diseases. Thus, a better understanding of the similarities between the aging process and neurodegenerative diseases at the cellular and molecular level may reveal better understanding of this detrimental relationship. In the present study, we mined publicly available gene expression datasets from healthy individuals and patients affected by neurodegenerative diseases (Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease) across a broad age spectrum and compared those with mouse aging and mouse cell-type specific gene expression profiles. We performed weighted gene co-expression network analysis (WGCNA) and found a gene network strongly related with both aging and neurodegenerative diseases. This network was significantly enriched with a microglial signature as imputed from cell type-specific sequencing data. Since mouse models are extensively used for the study of human diseases, we further compared these human gene regulatory networks with age-specific mouse brain transcriptomes. We discovered significantly preserved networks with both human aging and human disease and identified 17 shared genes in the top-ranked immune/microglia module, among which we found five human hub genes TYROBP, FCER1G, ITGB2, MYO1F, PTPRC, and two mouse hub genes Trem2 and C1qa. Taken together, these results support the hypothesis that microglia are key players involved in human aging and neurodegenerative diseases, and suggest that mouse models should be appropriate for studying these microglial changes in human.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

A Microglial Signature Directing Human Aging and Neurodegeneration-Related Gene Networks

et al. 2019

View full text Add to dashboard Cite

show abstract

“…In some studies, microdissected DA neurons from the SN were used (Cantuti‐Castelvetri et al., ; Elstner et al., , ; Simunovic et al., ; Kim et al., ; Briggs et al., ). Other brain regions investigated included the frontal cortex (Moran et al., ; Riley et al., ), Brodmann area 8 (BA8; Garcia‐Esparcia et al., ), BA9 (Zhang et al., ; Dumitriu et al., , ; Hoss et al., ), BA23 (Henderson‐Smith et al., ), putamen (Zhang et al., ; Vogt et al., ; Bossers et al., ; Naydenov et al., ; Botta‐Orfila et al., ; Nair & Ge, ), caudate nucleus (CN; Bossers et al., ), striatum (Miller et al., ; Riley et al., ), dorsal motor vagus nucleus (Lewandowski et al., ; Corradini et al., ), locus coeruleus (Botta‐Orfila et al., ; Corradini et al., ), occipital cortex (OC; Devine et al., ), posterior cingulate cortex (PCC; Stamper et al., ) and amygdala (Fig. ; Miñones‐Moyano et al., , ).…”

Section: Description Of Samples Used Across the 63 Original Studiesmentioning

confidence: 99%

“…Oligonucleotide microarrays were the most widely used platform for the transcriptomics studies on brain, particularly the Affymetrix Gene Array family of microarrays, which were used in 14 of the 33 studies (Table ; Table S1). Other platforms used were Affymetrix Exon Arrays (Botta‐Orfila et al., ,b), Illumina (Elstner et al., , ; Devine et al., ; Durrenberger et al., ), Agilent (Bossers et al., ; Dumitriu et al., ; Corradini et al., ) and GE Codelink (Miller et al., ). Notably, the RNA‐Seq technique was used in only three studies (Riley et al., ; Dumitriu et al., ; Henderson‐Smith et al., ).…”

Section: Transcriptomic Platforms Usedmentioning

confidence: 99%

A review of genome‐wide transcriptomics studies in Parkinson's disease

Borrageiro

Haylett

Seedat

et al. 2017

Eur J of Neuroscience

102

View full text Add to dashboard Cite

Parkinson's disease (PD) is a progressive and incurable neurodegenerative disorder. Although numerous genetic and environmental factors have been linked to the aetiology of PD the underlying pathobiology remains poorly understood, hampering the development of improved therapies. Transcriptomics has the potential to reveal significant insights into disease processes. In this review, we focused on published transcriptomics studies on PD with the aim of summarizing studies and identifying common biological pathways. A total of 96 articles were identified as follows: 12 meta-analyses, 21 re-analyses of existing data and 63 original studies. Of the 63 original studies, 33 were performed on brain tissue, 26 on blood, three on cerebrospinal fluid and one on skin. In the brain studies, altered pathways identified included those involved in dopamine metabolism, mitochondrial function, oxidative stress, protein degradation, neuroinflammation, vesicular transport and synaptic transmission. Studies on blood samples revealed alterations in pathways involved in immune function, inflammation, RNA processing, protein chaperones, mitochondrial function and programmed cell death. Limitations of these studies include small sample sizes (generally <40 cases/40 controls) and the application of widely varying statistical analysis and parameters. Only eight studies used the RNA-Seq technique. This review highlights the need for harmonization of transcriptomic approaches and the statistical analyses, and for the data to be deposited into publicly available databases in a standardized format for meta-analyses. Notably, the concordance of several pathways such as mitochondrial function, protein degradation and inflammation, identified in both blood and brain tissues, suggests that the disease process is systemic and not restricted to neurological tissues.

show abstract

“…Furthermore, transcriptome analysis has allowed for a better understanding in relation to genes or loci potentially associated with the disease. Several experiments conducted on post-mortem brain tissue of PD patients and related controls, mainly on SN whole tissue or DA neurons obtained with laser capture microdissection (LMD), demonstrated differential gene expression profiles between PD patients and controls [ 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 ].…”

Section: Introductionmentioning

confidence: 99%

Sex-Specific Transcriptome Differences in Substantia Nigra Tissue: A Meta-Analysis of Parkinson’s Disease Data

Mariani

Lombardini

Facchin

et al. 2018

Genes

View full text Add to dashboard Cite

Parkinson’s disease (PD) is one of the most common progressive neurodegenerative diseases. Clinical and epidemiological studies indicate that sex differences, as well as genetic components and ageing, can influence the prevalence, age at onset and symptomatology of PD. This study undertook a systematic meta-analysis of substantia nigra microarray data using the Transcriptome Mapper (TRAM) software to integrate and normalize a total of 10 suitable datasets from multiple sources. Four different analyses were performed according to default parameters, to better define the segments differentially expressed between PD patients and healthy controls, when comparing men and women data sets. The results suggest a possible regulation of specific sex-biased systems in PD susceptibility. TRAM software allowed us to highlight the different activation of some genomic regions and loci involved in molecular pathways related to neurodegeneration and neuroinflammatory mechanisms.

show abstract

Complex Network-Driven View of Genomic Mechanisms Underlying Parkinson’s Disease: Analyses in Dorsal Motor Vagal Nucleus, Locus Coeruleus, and Substantia Nigra

Cited by 33 publications

References 125 publications

A Microglial Signature Directing Human Aging and Neurodegeneration-Related Gene Networks

A Microglial Signature Directing Human Aging and Neurodegeneration-Related Gene Networks

A review of genome‐wide transcriptomics studies in Parkinson's disease

Sex-Specific Transcriptome Differences in Substantia Nigra Tissue: A Meta-Analysis of Parkinson’s Disease Data

Contact Info

Product

Resources

About