Abstract
Background: Neurodegeneration is a progressive/irreversible loss of neurons, building blocks of our nervous system. Their degeneration gradually collapses the entire structural and functional system manifesting in myriads of clinical disorders categorized as Neurodegenerative Disorders (NDs) such as Alzheimer's Disease, (AD), Parkinson’s Disease (PD), Frontotemporal Dementia (FTD) and Amyotrophic Lateral Sclerosis (ALS). NDs are characterized by a puzzling interplay of molecular and cellular defects affecting subset of neuronal populations in specific affected brain areas.
Objective: In present study, comparative in silico analysis was performed by utilizing gene expression datasets of AD, PD, FTD and ALS to identify potential common features to gain insights into complex molecular pathophysiology of the selected NDs.
Methods: Gene expression data of four disorders were subjected to the identification of Differential Gene Expression (DEG) and their mapping on biological processes, KEGG pathways and molecular functions. Detailed comparative analysis was performed to highlight the common grounds of these disorders at various stages.
Results: Astoundingly, 106 DEGs were found to be common across all disorders. Alongwith in total 100 GO terms and 7 KEGG pathways were found to be significantly enriched across all disorders. EGFR, CDC42 and CREBBP have been identified as the significantly interacting nodes in gene-gene interaction and in Protein-Protein Interaction (PPI) network as well. Furthermore, interaction of common DEGs targets with miRNA’s has been scrutinized.
Conclusion: The complex molecular underpinnings of these disorders are currently elusive. Despite heterogeneous clinical and pathological expressions, common features have been recognized in many NDs which provide evidence of their convergence.
Keywords: Neurodegeneration, Alzheimer's, Parkinson's, Frontotemporal dementia, Amyotrophic lateral sclerosis, Dysregulated genes, Retrograde endocannabinoid signaling, Calcium signaling.
Graphical Abstract
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