Decoding Common Features of Neurodegenerative Disorders: From Differentially Expressed Genes to Pathways

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 dis-orders 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 in-teraction 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.

Disruption of Tip60 HAT mediated neural histone acetylation homeostasis is an early common event in neurodegenerative diseases

“…Despite exhibiting a wide range of molecular and phenotypic heterogeneity, NDs share some general characteristics, such as protein misfolding and aggregation, mitochondrial dysfunction, dysregulation of similar molecular/cellular pathways and loss of chromatin dynamics 2 – 4 . Together, these similarities support convergence of heterogeneous NDs, and better insight into these common links will help target multiple NDs with potential unifying therapeutics 3 , 4 .…”

“…Depending on the specific subset of neurons and/or the area of nervous system severely affected, NDs vary with respect to the molecular pathways underlying the disease and the subsequent clinical manifestations 1 . Despite exhibiting a wide range of molecular and phenotypic heterogeneity, NDs share some general characteristics, such as protein misfolding and aggregation, mitochondrial dysfunction, dysregulation of similar molecular/cellular pathways and loss of chromatin dynamics [2][3][4] . Together, these similarities support convergence of heterogeneous NDs, and better insight into these common links will help target multiple NDs with potential unifying therapeutics 3,4 .…”

Regulation of Social Stress and Neural Degeneration by Activity-Regulated Genes and Epigenetic Mechanisms in Dopaminergic Neurons

“…A recent study searching for genes differentially expressed in Parkinson’s, Alzheimer’s, frontotemporal dementia, and amyotrophic lateral sclerosis found three major hub genes, including EGFR, CDC42, and CREBBP. CREBBP is a histone acetylase that partners with CREB to increase histone acetylation and gene expression at CREB-binding sites [ 70 ]. Another intersectional study of genes differentially expressed in Parkinson’s and Huntington’s diseases implicated targets of CREB signaling [ 71 ].…”

In vitro Characterization of Gut Microbiota-Derived Bacterial Strains With Neuroprotective Properties

“…Neurodegenerative diseases (NDDs) such as Parkinson’s disease (PD) and Alzheimer’s disease (AD) are disabling, incurable disorders, often associated with aging. Progressive and irreversible loss of neurons, neuroinflammation and degeneration of cellular functions and structures often associated with oxidative stress, are common features of NDDs (Habib et al, 2018). NDDs have a profound impact on the life expectancy of individuals and the socio-economy of the world population (Group, 2017).…”