Current Topics in Medicinal Chemistry - Volume 19, Issue 7, 2019

Background: Alzheimer’s Disease (AD), a multifaceted disorder, involves complex pathophysiology and plethora of protein-protein interactions. Thus such interactions can be exploited to develop anti-AD drugs. Objective: The interaction of dynamin-related protein 1, cellular prion protein, phosphoprotein phosphatase 2A and Mint 2 with amyloid β, etc., studied recently, may have critical role in progression of the disease. Our objective has been to review such studies and their implications in design and development of drugs against the Alzheimer’s disease. Methods: Such studies have been reviewed and critically assessed. Results: Review has led to show how such studies are useful to develop anti-AD drugs. Conclusion: There are several PPIs which are current topics of research including Drp1, Aβ interactions with various targets including PrPC, Fyn kinase, NMDAR and mGluR5 and interaction of Mint2 with PDZ domain, etc., and thus have potential role in neurodegeneration and AD. Finally, the multi-targeted approach in AD may be fruitful and opens a new vista for identification and targeting of PPIs in various cellular pathways to find a cure for the disease.

Background: Identification of Protein-Protein Interactions (PPIs) is a major challenge in modern molecular biology and biochemistry research, due to the unquestionable role of proteins in cells, biological process and pathological states. Over the past decade, the PPIs have evolved from being considered a highly challenging field of research to being investigated and examined as targets for pharmacological intervention. Objective: Comprehension of protein interactions is crucial to known how proteins come together to build signalling pathways, to carry out their functions, or to cause diseases, when deregulated. Multiplicity and great amount of PPIs structures offer a huge number of new and potential targets for the treatment of different diseases. Methods: Computational techniques are becoming predominant in PPIs studies for their effectiveness, flexibility, accuracy and cost. As a matter of fact, there are effective in silico approaches which are able to identify PPIs and PPI site. Such methods for computational target prediction have been developed through molecular descriptors and data-mining procedures. Results: In this review, we present different types of interactions between protein-protein and the application of in silico methods for design and development of drugs targeting PPIs. We described computational approaches for the identification of possible targets on protein surface and to detect of stimulator/ inhibitor molecules. Conclusion: A deeper study of the most recent bioinformatics methodologies for PPIs studies is vital for a better understanding of protein complexes and for discover new potential PPI modulators in therapeutic intervention.

Background: Phosphodiesterases (PDEs) are enzymes that play a key role in terminating cyclic nucleotides signalling by catalysing the hydrolysis of 3’, 5’- cyclic adenosine monophosphate (cAMP) and/or 3’, 5’ cyclic guanosine monophosphate (cGMP), the second messengers within the cell that transport the signals produced by extracellular signalling molecules which are unable to get into the cells. However, PDEs are proteins which do not operate alone but in complexes that made up of a many proteins. Objective: This review highlights some of the general characteristics of PDEs and focuses mainly on the Protein-Protein Interactions (PPIs) of selected PDE enzymes. The objective is to review the role of PPIs in the specific mechanism for activation and thereby regulation of certain biological functions of PDEs. Methods: The article discusses some of the PPIs of selected PDEs as reported in recent scientific literature. These interactions are critical for understanding the biological role of the target PDE. Results: The PPIs have shown that each PDE has a specific mechanism for activation and thereby regulation a certain biological function. Conclusion: Targeting of PDEs to specific regions of the cell is based on the interaction with other proteins where each PDE enzyme binds with specific protein(s) via PPIs.