Unlocking the concealed targets using system biology mapping for Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) constitutes a neural loss in histology of brain with involvement of complex genomic and environmental factors. Accumulation of amyloid beta (Aß) peptide and phosphorylated tau are indicative of progression and cognitive decline. Hence an understanding of the underlying biological pathways and targets along with associated mechanisms would be useful for the development of improved therapeutics for treating AD. In the present work, we aim to identify concealed targets for developing first line therapeutics and repositioning of validated targets as well as FDA- approved drugs using a system biology approach. METHODS: We have collated information pertaining to the biological targets as well as the approved drugs, from scientific literature and patents. RESULTS: In all, the imbalance in the functioning of around 79 proteins and genes were identified to be involved in Alzheimer's cascade. Amongst them, around 21 targets were found to be under therapeutic consideration for AD. Of the remaining, around 17 targets were reported as potential targets for AD, although they are under researcher's attention for other physio-pathological conditions. The analysis further revealed that ˜41 therapeutic targets are pharmacologically concealed but structurally validated targets and may constitute as potential therapeutic candidate for future drug discovery for AD. CONCLUSION: The biological pathway vs. drug mapping provides a complete overview about underlying biological pathways, therapeutic targets (explored and concealed), associated mechanisms, existing therapeutics and the information pertaining to molecules currently under active drug development for further drug discovery and drug re-positioning/repurposing approaches for AD management.

An update on disease modifying antirheumatic drugs.

Disease modifying antirheumatic drugs (DMARDs) is a category of drugs which is used as medication in various arthritic conditions to arrest the progression of disease along with relief from pain. About 83% of population worldwide uses DMARDs. Withdrawal of COX-2 inhibitors because of cardiovascular side effects and short-term action associated with glucocorticoids provided a motivation for development of newer DMARDs. Currently non- biological DMARDs like methotrexate, sulfasalazine, hydroxychloroquine and azathioprine serve the purpose of relieving pain and inhibiting the progression of disease. Biological DMARDs like toclizumab, adalimumab, infliximab, golimumab and abatacept have shown more efficacy and lesser side effects as compared to non- biological DMARDs but their access to patient is less because of higher cost. DMARDs act by different mechanisms against inflammation like inhibition of tumor necrosis factor, suppression of IL-1 and TNF-α, induction of apoptosis of inflammatory cells, by increasing chemotactic factors, inhibition of purine synthesis, pyrimidine metabolism or purine embolism. DMARDs have important applications in diseases like rheumatoid arthritis, Crohn's disease, juvenile idiopathic arthritis, psoriatic arthritis and myasthenia gravis. Present review mainly focuses on DMARDs and their clinical applications giving an overview of their mechanism of action, pharmacokinetic properties, advantages over conventional therapies, shortcomings and recent trends.