Integrated analysis of mRNA expression profiling in Parkinson’s Disease

Abstract

Departmental sources Background: Parkinson's disease (PD) is a degenerative neurologic disease. This study aimed to undertake bioinformatics analysis using the publicly available Gene Expression Omnibus (GEO) database to integrate mRNA expression data from patients with PD and to compare differentially expressed genes (DEGs) in tissue from the substantia nigra and whole blood from patients with PD and normal controls. Material/Methods: Integrated network analysis included GEO datasets to identify DEGs in the substantia nigra and whole blood of patients with PD. Bioinformatics analysis was used to identify the roles of the DEGs and included the development of protein-protein interaction (PPI) networks and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Expression levels of DEGs were validated using GSE100054. Results: In patients with PD, there were 1,076 upregulated DEGs and 1,075 down-regulated DEGs in the substantia nigra tissue, and 699 upregulated and 930 down-regulated DEGs in whole blood samples. The apoptotic process, the mitogen-activated protein kinase (MAPK) signaling pathway, the Wnt signaling pathway, and the Notch signaling pathway were significantly enriched in DEGs in the substantia nigra in PD. In both the substantia nigra and whole blood, the most common DEGs were significantly enriched in lysosomes, PD, Alzheimer's disease, Huntington's disease. SORT1 and CRYAB were the hub proteins in the network of the substantia nigra; PSMA1 and SDHA were the hub proteins in the network of whole blood in PD. Conclusions: DEGs, including SORT1, CRYAB, PSMA1, and SDHA may have roles in the pathogenesis of PD through the MAPK, Wnt, and Notch signaling pathways.

Molecular Features of Parkinson's Disease in Patient‐Derived Midbrain Dopaminergic Neurons

“…2C). Reduced expression of ALDH1A1 in the substantia nigra of patients with PD 39 is consistent with our results (Fig. 2D).…”

The Occurrence of Alzheimer’s Disease and Parkinson’s Disease in Individuals With Osteoporosis: A Longitudinal Follow-Up Study Using a National Health Screening Database in Korea

“…Research has identified several genetic or environmental factors that may contribute to the neurodegeneration associated with osteoporotic conditions. First, Wnt/β-catenin signaling has attracted attention because aberrant Wnt/β-catenin signaling has been reported to affect both osteoporosis and neurodegenerative diseases, including Parkinson’s and Alzheimer’s diseases (Li et al, 2013 ; Folke et al, 2019 ; Wang and Wang, 2020 ). Approximate percentages of patients with AD, PD, or osteoporosis who have a pathogenic variant of Wnt/β-catenin signaling have not yet been established.…”

“…Over the last two decades, epidemiological studies have highlighted the potential link between osteoporosis and the risk of neurodegenerative disease (Yaffe et al, 1999;Tan et al, 2005;Zhou et al, 2011;Chang et al, 2014;Roos, 2014;Amouzougan et al, 2017;Kostev et al, 2018;Feng et al, 2021). Experimental evidence supports that molecular alterations and chemical exposure mediate the pathogenic changes associated with AD and PD in osteoporotic animal models (Li et al, 2013(Li et al, , 2014Calabrese et al, 2016;Folke et al, 2019;Wang and Wang, 2020;Abdul-Latif et al, 2021;Jiang et al, 2021), and researchers assume they may share some central mechanisms. While the majority of epidemiological studies have focused on the effect of osteoporosis on the risk of AD or dementia (Yaffe et al, 1999;Tan et al, 2005;Zhou et al, 2011;Chang et al, 2014;Roos, 2014;Amouzougan et al, 2017;Kostev et al, 2018), data for the relation to PD risk are scarce (Feng et al, 2021).…”

Sortilin acts as an endocytic receptor for α‐synuclein fibril

“…Intriguingly, transcriptome analyses of postmortem brain tissue samples obtained by LCM have revealed spatiotemporal changes in the expression levels of various genes associated with PD 36,41 . Furthermore, recent bioinformatics analysis using publicly available Gene Expression Omnibus database, comparing differentially expressed genes in PD patients and normal controls, revealed that sortilin is upregulated in the substantia nigra of PD and serves as a hub molecule in the protein–protein interaction network 42 . Given this situation, we used a publicly available RNA‐seq dataset of neuromelanin‐containing midbrain dopaminergic neurons obtained from the brain samples of PD and ILBD to evaluate the expression profile of sortilin during disease progression (Figure 6C,D).…”