Current Drug Targets - Volume 23, Issue 12, 2022

Background: Coronavirus disease 2019 (COVID-19) is currently rampant worldwide, resulting in unpredictable harm to humans. High blood levels of cytokines and chemokines have been marked in patients with COVID-19 infection, leading to cytokine storm syndrome. Cytokine storms are violent inflammatory immune responses that reveal the devastating effect of immune dysregulation and the critical role of an effective host immune response. Methods: Scientometric analysis summarizes the literature on cytokine storms in recent decades and provides a valuable and timely approach to tracking the development of new trends. This review summarizes the pathogenesis and treatment of diseases associated with cytokine storms comprehensively based on scientometric analysis. Results: Field distribution, knowledge structure, and research topic evolution correlated with cytokine storms are revealed, and the occurrence, development, and treatment of disease relevant to cytokine storms are illustrated. Conclusion: Cytokine storms can be induced by pathogens and iatrogenic causes and can also occur in the context of autoimmune diseases and monogenic diseases as well. These reveal the multidisciplinary nature of cytokine storms and remind the complexity of the pathophysiological features, clinical presentation, and management. Overall, this scientometric study provides a macroscopic presentation and further direction for researchers who focus on cytokine storms.

Background: Human infectious diseases caused by bacteria are a worldwide health problem due to the increased resistance of these microorganisms to conventional antibiotics. For this reason, the identification of novel molecular targets and the discovery of new antibacterial compounds are urgently required. Metalo-aminopeptidases are promising targets in bacterial infections. They participate in crucial processes for bacterial growth and pathogenesis, such as protein and peptide degradation to supply amino acids, protein processing, access to host tissues, cysteine supply for redox control, transcriptional regulation, site-specific DNA recombination, and hydrogen sulfide production. Although several of these enzymes are not essential, they are required for virulence and maximal growth in conditions of nutrient limitation and high temperatures. Objective: In this review, we describe the structural, functional, and kinetic properties of some examples of bacterial metalo-aminopeptidases, in the context of their use as antibacterial targets. In addition, we present some inhibitors reported for these enzymes. Conclusion: It is necessary to conduct a meticulous work to validate these peptidases as good/bad targets and to identify inhibitors with potential therapeutic use.

Activation of the receptor for advanced glycation end products (RAGE) has been shown to play an active role in the development of multiple neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and Amyotrophic Lateral Sclerosis. Although originally identified as a receptor for advanced glycation end products, RAGE is a pattern recognition receptor able to bind multiple ligands. The final outcome of RAGE signaling is defined in a context and cell type specific manner and can exert both neurotoxic and neuroprotective functions. Contributing to the complexity of the RAGE signaling network, different RAGE isoforms with distinctive signaling capabilities have been described. Moreover, multiple RAGE ligands bind other receptors and RAGE antagonism can significantly affect their signaling. Here, we discuss the outcome of celltype specific RAGE signaling in neurodegenerative pathologies. In addition, we will review the different approaches that have been developed to target RAGE signaling and their therapeutic potential. A clear understanding of the outcome of RAGE signaling in a cell type- and disease-specific manner would contribute to advancing the development of new therapies targeting RAGE. The ability to counteract RAGE neurotoxic signaling while preserving its neuroprotective effects would be critical for the success of novel therapies targeting RAGE signaling.