Comparative Analysis Of Gene Interaction Networks And Drug Targets Among Three Neurodegenerative Diseases

Neurodegenerative diseases(NDDs)are a type of disorders that are characterized by the progressive degeneration of the structure and function of the central nervous system or peripheral nervous system.Common neurodegenerative diseases include Alzheimer's disease(AD),Parkinson's disease(PD)and Multiple sclerosis(MS).These diseases have brought great troubles to patients and their families,also caused a great social and economic burden,and become a global health problem.According to the pathological manifestations,neurodegenerative diseases can be divided into three typical types,namely,cognitive-disabled type,mobility disorder and inflammatory neurodegenerative diseases,and AD,PD and MS are corresponding representative of those three kinds of NDDs.Although the study of these diseases has become a hot topic in recent years,but what are the underline molecular links among different NDDs? Also,the similarities and differences in development mechanisms among these NDDs are still unclear.In this paper,125 AD-related genes,185 PD-related genes and 288 MS-related genes were screened by literature search and database mining.By comparing the genes related to different NDDs,nine genes were found commonly in three neurodegenerative diseases(ACE_HUMAN,APOE_HUMAN,ESR1_HUMAN,HFE_HUMAN,IL10_HUMAN,IL8_HUMAN,MTHR_HUMAN,PON1_HUMAN and TNFA_HUMAN respectively).Subsequently,by analyzing the GO function of the neurodegenerative disease related genes,we found that a total of 37 GO terms were significantly enriched in the three neurodegenerative diseases;They are mainly involved in biologically synthesized with reactive oxygen species,the response of cells to biological stimuli,Lipid-related pathways,inflammation,aging and so on.Then,the pathway was annotated and enrichment analysis was performed with databases including KEGG,Reactome,BioCyc and PANTHER.The results indicated that two signal pathways,respectively rheumatoid arthritis(Rheumatoid arthritis,RA)and inflammatory bowel disease(Inflammatory bowel disease,IBD),were significantly enriched in all the three neurodegenerative diseases.Moreover,we compared the three diseases from the network level and obtained 25 key nodes.It provided effective hints and data for the future design of drugs that also acted on the three diseases simultaneously.Finally,the known drugs and corresponding target genes of the three kinds of NDDs were collected and analyzed.The results showed that their corresponding KEGG pathways overlaped largely,and 37 common pathways harboring drug targets were involved;and there is no known drug for AD specific pathways.In conclusion,this study analyzed the related genes,signaling pathways,protein interaction networks and corresponding drug target genes of these NDDs from many different perspectives.It has laid a theoretical foundation for further researches on the molecular mechanism of neurodegenerative diseases and provides hits for exploring the relationship among neurodegenerative diseases and drug development.