Bioinformatics Approach to Identify Significant Biomarkers, Drug Targets Shared Between Parkinson’s Disease and Bipolar Disorder: A Pilot Study

Abstract

Parkinson’s disease (PD) is a neurodegenerative disorder responsible for shaking, rigidity, and trouble in walking and patients’ coordination ability and physical stability deteriorate day by day. Bipolar disorder (BD) is a psychiatric disorder which is the reason behind extreme shiftiness in mood, and frequent mood inversion may reach too high called mania. People with BD have a greater chance of developing PD during the follow-up period. A lot of work has been done to understand the key factors for developing these 2 diseases. But the molecular functionalities that trigger the development of PD in people with BD are not clear yet. In our study, we are intended to identify the molecular biomarkers and pathways shared between BD and PD. We have investigated the RNA-Seq gene expression data sets of PD and BD. A total of 45 common unique genes (32 up-regulated and 13 down-regulated) abnormally expressed in both PD and BD were identified by applying statistical methods on the GEO data sets. Gene ontology (GO) and BioCarta, KEGG, and Reactome pathways analysis of these 45 common dysregulated genes identified numerous altered molecular pathways such as mineral absorption, Epstein-Barr virus infection, HTLV-I infection, antigen processing, and presentation. Analysis of protein-protein interactions revealed 9 significant hub-proteins, namely RPL21, RPL34, CKS2, B2M, TNFRSF10A, DTX2, HLA-B, ATP2A3, and TAPBP. Significant transcription factors (IRF8, SPI1, RUNX1, and FOXA1) and posttranscriptional regulator microRNAs (hsa-miR-491-3p and hsa-miR-1246) are also found by analyzing gene-transcription factors and gene-miRNAs interactions, respectively. Protein-drug interaction analysis revealed hub-protein B2M’s interaction with molecular drug candidates like N-formylmethionine, 3-indolebutyric acid, and doxycycline. Finally, a link between pathological processes of PD and BD is identified at transcriptional level. This study may help us to predict the development of PD among the people suffering from BD and gives some clue to understand significant pathological mechanisms.

Identification and Experimental Validation of Parkinson’s Disease with Major Depressive Disorder Common Genes

“…A meta-analysis of the PD public dataset showed that SPI1 is the TF of the hub gene (53). Meanwhile, SPI1 is also an important TF of the hub gene in PD with bipolar disorder (54). Besides, a study has demonstrated that SPI1 is a key gene associated with postpartum depression (PPD)(55).…”

Integrative multi-omics and systems bioinformatics in translational neuroscience: A data mining perspective

“…Interestingly, the study revealed an overlap between central and peripheral transcriptomic signatures in PD that are characterized by anomalies in exocytosis and specific genes related to the SNARE complex including vesicle-associated membrane protein 2 ( VAMP2 ), syntaxin 1A ( STX1A ), and p21-activated kinase 1 ( PAK1 ) [ 61 ]. In a separate PD study making use of RNA-seq datasets from the GEO database, several genes including RPL21 , RPL34 , CKS2 , B2M , TNFRSF10A , DTX2 , and HLA-B , have been shown to be upregulated in PD brain tissues [ 62 ]. In MS, a data mining study analyzing RNA-seq datasets from the GEO database has reported that inactive MS brain lesions contain significantly more M2 macrophages compared to normal white matter controls [ 63 ].…”

Nutritional Psychiatry Integrated Framework: Exploration of Nutrition and Co-occurring Bipolar Disorder and Post-traumatic Stress Disorder

“…Many people diagnosed with bipolar disorder have rapid mood swings among other clinical symptomology. Bipolar disorder is categorized into bipolar disorder I and bipolar II which involves recurrent episodes of depressive and manic symptoms [42][43][44]. A diagnosis of bipolar disorder is controversial and some people with bipolar disorder are originally misdiagnosed or underdiagnosed [7,45].…”