Decoding genetic and pathophysiological mechanisms in amyotrophic lateral sclerosis and primary lateral sclerosis: A comparative study of differentially expressed genes and implicated pathways in motor neuron disorders
| Author | R, Hephzibah Cathryn |
| Author | Datta, Ankur |
| Author | S, Udhaya Kumar |
| Author | Zayed, Hatem |
| Author | D, Thirumal Kumar |
| Author | C, George Priya Doss |
| Available date | 2024-10-28T10:44:13Z |
| Publication Date | 2024 |
| Publication Name | Advances in Protein Chemistry and Structural Biology |
| Resource | Scopus |
| ISSN | 18761623 |
| Abstract | Motor Neuron Disorders (MNDs), characterized by the degradation and loss of function of motor neurons, are recognized as fatal conditions with limited treatment options and no known cure. The present study aimed to identify the pathophysiological functions and affected genes in patients with MNDs, specifically Amyotrophic Lateral Sclerosis (ALS) and Primary Lateral Sclerosis (PLS). The GSE56808 dataset comprised three sample groups: six patients diagnosed with ALS (GSM1369650, GSM1369652, GSM1369654, GSM1369656, GSM1369657, GSM1369658), five patients diagnosed with PLS (GSM1369648, GSM1369649, GSM1369653, GSM1369655, GSM1369659), and six normal controls (GSM1369642, GSM1369643, GSM1369644, GSM1369645, GSM1369646, and GSM1369647). The application of computational analysis of microarray gene expression profiles enabled us to identify 346 significantly differentially expressed genes (DEGs), 169 genes for the ALS sample study, and 177 genes for the PLS sample study. Enrichment was carried out using MCODE, a Cytoscape plugin. Functional annotation of DEGs was carried out via ClueGO/CluePedia (v2.5.9) and further validated via the DAVID database. NRP2, SEMA3D, ROBO3 and, CACNB1, CACNG2 genes were identified as the gene of interest for ALS and PLS sample groups, respectively. Axonal guidance (GO:0007411) and calcium ion transmembrane transport (GO:0070588) were identified to be some of the significantly dysregulated gene ontology (GO) terms, with arrhythmogenic right ventricular cardiomyopathy (KEGG:05412) to be the top relevant KEGG pathway which is affected in MND patients. ROBO3 gene was observed to have distinctive roles in ALS and PLS-affected patients, hinting towards the differential progression of ALS from PLS. The insights derived from our comprehensive analysis accentuate the distinct variances in the underlying molecular pathogenesis of ALS and PLS. Further research should investigate the mechanistic roles of the identified DEGs and molecular pathways, leading to potential targeted therapies for ALS and PLS. |
| Sponsor | The authors would like to thank the management of the Vellore Institute of Technology (VIT), Vellore, Tamil Nadu, India, and Qatar University, Qatar, for providing the necessary facilities and encouragement to carry out this work. No funding agency was involved in the present study. AD, HCR, UKS, TKD, and GPDC were involved in the study design. AD, HCR, UKS, TKD, and HZ were involved in acquiring, analyzing, interpreting the results, and drafting the manuscript. GPDC supervised the entire study and edited the manuscript. All authors edited and approved the submitted version of the article. The authors declare that the study has no conflict of interest. |
| Language | en |
| Publisher | Elsevier |
| Subject | Amyotrophic lateral sclerosis Functional enrichment Gene networking Motor neuron disorders Primary lateral sclerosis |
| Type | Article |
| Pagination | 177-201 |
| Volume Number | 141 |
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