Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Objective: Parkinson's disease (PD) is one of the most common neurodegenerative diseases. This study aims to screen specific modules and key genes related to PD.
Methods: Gene expression profile data GSE6613 and GSE22491 were downloaded from the Gene Expression Omnibus database. The significantly differentially expressed genes (DEGs) in different datasets were screened, followed by gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The Weighted Gene Co-expression Network Analysis (WGCNA) was used to screen disease-related modules that are significantly stable across datasets. The protein-protein interaction network was constructed using the DEGs in the stable module obtained and preservation modules. Finally, the hub genes directly related to PD were screened.
Results: A total of 179 DEGs with the same significant difference direction were screened. The enrichment analysis of GO and KEGG pathways showed that 20 significantly related GO biological processes and 9 KEGG signaling pathways were screened. A total of three highly conservative modules were detected in the WGCNA network. Finally, three significant PD-related KEGG pathways screened from the Comparative Toxicogenomics Database were identified, including neuroactive ligand-receptor interaction (CRHR2, CTSG, GRIN1, GRIN2D, LPAR4 and P2RX3), amyotrophic lateral sclerosis (BCL2, GRIN1 and GRIN2D) and alcoholism (CAMKK2, GRIN1, GRIN2D and SLC18A2). Key genes, such as SLC18A2, GRIN1 and GRIN2D, may be potential candidate genes for PD progression.
Conclusions: Our findings indicate that SLC18A2, GRIN1 and GRIN2D may play an important role in the pathogenesis of PD.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1097/WNR.0000000000001695 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Ligand distances as key predictors of pathogenicity and function in NMDA receptors.
Hum Mol Genet
January 2025
Department of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, 1133 John Freeman Blvd, Houston, TX 77030, United States.
Genetic variants in the genes GRIN1, GRIN2A, GRIN2B, and GRIN2D, which encode subunits of the N-methyl-D-aspartate receptor (NMDAR), have been associated with severe and heterogeneous neurologic and neurodevelopmental disorders, including early onset epilepsy, developmental and epileptic encephalopathy, intellectual disability, and autism spectrum disorders. Missense variants in these genes can result in gain or loss of the NMDAR function, requiring opposite therapeutic treatments. Computational methods that predict pathogenicity and molecular functional effects of missense variants are therefore crucial for therapeutic applications.
View Article and Find Full Text PDFGenetic variants in genes , , , and , which encode subunits of the N-methyl-D-aspartate receptor (NMDAR), have been associated with severe and heterogeneous neurologic diseases. Missense variants in these genes can result in gain or loss of the NMDAR function, requiring opposite therapeutic treatments. Computational methods that predict pathogenicity and molecular functional effects are therefore crucial for accurate diagnosis and therapeutic applications.
View Article and Find Full Text PDFLoss of Grin2a causes a transient delay in the electrophysiological maturation of hippocampal parvalbumin interneurons.
Commun Biol
September 2023
Department of Pharmacology and Chemical Biology, Emory University School of Medicine, Atlanta, GA, 30322, USA.
N-methyl-D-aspartate receptors (NMDARs) are ligand-gated ionotropic glutamate receptors that mediate a calcium-permeable component to fast excitatory neurotransmission. NMDARs are heterotetrameric assemblies of two obligate GluN1 subunits (GRIN1) and two GluN2 subunits (GRIN2A-GRIN2D). Sequencing data shows that 43% (297/679) of all currently known NMDAR disease-associated genetic variants are within the GRIN2A gene, which encodes the GluN2A subunit.
View Article and Find Full Text PDFObjective: Parkinson's disease (PD) is one of the most common neurodegenerative diseases. This study aims to screen specific modules and key genes related to PD.
Methods: Gene expression profile data GSE6613 and GSE22491 were downloaded from the Gene Expression Omnibus database.
Disease-associated GRIN protein truncating variants trigger NMDA receptor loss-of-function.
Hum Mol Genet
February 2021
Neuroscience Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, 08908 Barcelona, Spain.
De novo GRIN variants, encoding for the ionotropic glutamate NMDA receptor subunits, have been recently associated with GRIN-related disorders, a group of rare paediatric encephalopathies. Current investigational and clinical efforts are focused to functionally stratify GRIN variants, towards precision therapies of this primary disturbance of glutamatergic transmission that affects neuronal function and brain. In the present study, we aimed to comprehensively delineate the functional outcomes and clinical phenotypes of GRIN protein truncating variants (PTVs)-accounting for ~20% of disease-associated GRIN variants-hypothetically provoking NMDAR hypofunctionality.
View Article and Find Full Text PDF