The Gut-Brain Axis: Two Ways Signaling in Parkinson's Disease.

Parkinson's disease (PD) is a chronic, progressive and second most prevalent neurological disorder affecting the motor system. Cardinal motor impairment and α-synucleinopathy are the characteristic features of PD. Recently, it has been identified that the gut-brain axis is substantially regulated by the gut microbiome (GM) through an immunological, neuroendocrine, and neural mechanism. However, disturbance in the gut-microbiome-brain axis in PD might proceed to gastrointestinal manifestations intermittently leading to the motor system and the PD pathogenesis itself. The gut microbial toxins may induce the production of α-synuclein (α-syn) aggregates in the enteric nervous system (ENS), which may proliferate and propagate in a prion-like-manner through the vagus nerve to the central nervous system (CNS); supporting the hypothesis that, GM might play a pivotal role in PD pathogenesis. Overstimulated innate immune system due to intestinal bacterial overgrowth or gut dysbiosis and the enhanced intestinal permeability may persuade systemic inflammation, while the activation of enteric glial cells and enteric neurons may contribute to α-synucleinopathy. Gut microbiota can bear a significant impact on neurological outcomes such as learning, memory and cognition. In this review paper, we summarize how the alterations in gut microbiota and ENS inflammation are associated with PD pathogenesis. The evidence supporting the causative role played by gut-associated dysbiosis and microbial byproducts, in the onset of PD is also discussed. We have highlighted the landmark discoveries in the field of PD particularly focusing on the gut-brain axis. A better comprehension of the interaction between the gut-brain axis, gut microbiota, and PD can usher in novel therapeutic and diagnostic approaches.

Protein Interaction Studies for Understanding the Tremor Pathway in Parkinson's Disease.

BACKGROUND: Tremor is one of the most noticeable features, which occurs during the early stages of Parkinson's Disease (PD). It is one of the major pathological hallmarks and does not have any interpreted mechanism. In this study, we have framed a hypothesis and deciphered protein- protein interactions between the proteins involved in impairment in sodium and calcium ion channels and thus cause synaptic plasticity leading to a tremor. METHODS: Literature mining for retrieval of proteins was done using Science Direct, PubMed Central, SciELO and JSTOR databases. A well-thought approach was used, and a list of differentially expressed proteins in PD was collected from different sources. A total of 71 proteins were retrieved, and a protein interaction network was constructed between them by using Cytoscape.v.3.7. The network was further analysed using the BiNGO plugin for retrieval of overrepresented biological processes in Tremor-PD datasets. Hub nodes were also generated in the network. RESULTS: The Tremor-PD pathway was deciphered, which demonstrates the cascade of protein interactions that might lead to tremors in PD. Major proteins involved were LRRK2, TUBA1A, TRAF6, HSPA5, ADORA2A, DRD1, DRD2, SNCA, ADCY5, TH, etc. Conclusion: In the current study, it is predicted that ADORA2A and DRD1/DRD2 are equally contributing to the progression of the disease by inhibiting the activity of adenylyl cyclase and thereby increases the permeability of the blood-brain barrier, causing an influx of neurotransmitters and together they alter the level of dopamine in the brain which eventually leads to tremor.

Differential Expression of TOM34, AL1A1, PADI2 and KLRBA in NNK Induced Lung Cancer in Wistar Rats and their Implications.

BACKGROUND: Lung cancer is the most common cancer with a high mortality rate. The diagnosis only at advanced stages and lack of effective treatment are the main factors responsible for high mortality. Tobacco smoke is the major responsible factor for inflammation and tumor development in lungs. OBJECTIVE: The present study was carried out to identify differentially expressed proteins and elucidate their role in carcinogenesis. METHODS: The lung cancer was developed in Wistar rats by using NNK as carcinogen and cancer development was confirmed by histopathological examination. The 2D SDS PAGE was used to analyse total proteins and find out differentially expressed proteins in NNK treated lung tissue vis-a-vis control tissue. The findings of proteomic analysis were further validated by quantification of corresponding transcripts using Real Time PCR. Finally, Cytoscape was used to find out protein-protein interaction. RESULTS: The histopathological examinations showed neoplasia at 9th month after NNK treatment. The proteomic analysis revealed several differentially expressed proteins, four of which were selected for further studies. (TOM34, AL1A1, PADI2 and KLRBA) that were up regulated in NNK treated lung tissue. The real time analysis showed over expression of the genes coding for the selected proteins. Thus, the proteomic and transcriptomic data corroborate each other. Further, these proteins showed interaction with the members of NF-κB family and STAT3. CONCLUSION: We conclude that these proteins play a substantial role in the induction of lung cancer through NF-κB and STAT3 pathway. Therefore, these may have the potential to be used as therapeutic targets and for early detection of lung cancer.

Type 3 Diabetes: Cross Talk between Differentially Regulated Proteins of Type 2 Diabetes Mellitus and Alzheimer's Disease.

Type 3 Diabetes (T3D) is a neuroendocrine disorder that represents the progression of Type 2 Diabetes Mellitus (T2DM) to Alzheimer's disease (AD). T3D contributes in the increase of the total load of Alzheimer's patients worldwide. The protein network based strategies were used for the analysis of protein interactions and hypothesis was derived describing the possible routes of communications among proteins. The hypothesis provides the insight on the probable mechanism of the disease progression for T3D. The current study also suggests that insulin degrading enzyme (IDE) could be the major player which holds the capacity to shift T2DM to T3D by altering metabolic pathways like regulation of beta-cell development, negative regulation of PI3K/AKT pathways and amyloid beta degradation.