A comparative system‐level analysis of the neurodegenerative diseases

Abstract

Neurodegenerative diseases are disorders in the central nervous system with consequent progressive neurological symptoms including behavioral and cognitive disabilities. Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease, Parkinson's disease, multiple sclerosis, and schizophrenia are the most important and abundant neurodegenerative diseases that affect different parts of the brain. Detailed studies unveiled the molecular mechanisms and pathways affected in each of these disorders. The role of many genes has been documented in the onset and progression of each disease. Although many system-level approaches have been used to understand the exact cause of these diseases, there is no comparative analysis in this regard. Despite all differences in the molecular basis of these diseases, overlapping symptoms might indicate the involvement of the similar pathways and processes. Here, we have applied a system biology approach to uncover many aspects of main neurodegenerative diseases using microarray data obtained from 118 cases of postmortem brain samples. Our analysis has identified key genes that might contribute to the status of diseases. We have also compared the involved biological process and pathway between different disease to find possible similar mechanisms that exist in all of them. We also predicted potentially important transcription factors in each disease and predicted the core gene regulatory networks. We have provided a list of possible new key regulators that could be further explored and also discussed the role of these hub genes. The results of this study would be useful to develop new diagnostic strategies and also to find new drug targets.

Rps27a might act as a controller of microglia activation in triggering neurodegenerative diseases

“…Finally, they suggested a set of key genes that might contribute to all NDDs. Nevertheless, in this study, similar to the above mentioned, no pathway or gene was found to be in common across all six major NDDs [ 12 ].…”

“…One such characteristic is neuroinflammation which is associated with the immune system processes such as inflammation and immune response. Previously, a number of studies investigated the molecular factor(s) of such common changes [ 11 , 12 ]. However, to the best of our knowledge, no pathway or gene was reported to be in common across all major NDDs.…”

Neuroprotective Effects of Celastrol in Neurodegenerative Diseases-Unscramble Its Major Mechanisms of Action and Targets

“…Chronic neurodegenerative diseases mainly include AD, PD, ALS, HD, multiple sclerosis (MS) and spinocerebellar ataxias (SCAs), and acute neurodegenerative diseases mainly include stroke and TBI [ 33 , 34 ]. A multitude of factors contribute to the pathogenesis of neurodegenerative diseases, including accumulation of unfolded/misfolded proteins, abnormal cellular transport, neuro-inflammation, oxidative stress, mitochondrial dysfunction, excite-toxicity, intracellular Ca 2+ overload, abnormalities in the Genome, and apoptosis [ 35 , 36 ].…”

Biological databases and tools for neurological disorders

“…3, while Table 2 (Ref. [3,23,24,26,34,[44][45][46][47][48][49][50][51][52][53][54]) summarizes some of them. Further, the commonly used tools are discussed below.…”

“…Cytohubba provides analysis through eleven topological scoring methods to identify essential nodes in the network, it allows the construction of sub-network (or subgraph) for the essential nodes to enhance the further analysis of direct interaction with top-ranked nodes, this facilitated node retrieval function and extraction of user interesting network make Cytohubba better option than other tools like CentiScaPe [56]. Consequently, Cytohubba is used by researchers for topological analysis of various PPI networks in NDs [48].…”