Current Protein and Peptide Science - Volume 22, Issue 1, 2021

Diabetic neuropathy is referred to as a subsequential and debilitating complication belonging to type 1 and type 2 diabetes mellitus. It is a heterogeneous group of disorders with a particularly complex pathophysiology and also includes multiple forms, ranging from normal discomfort to death. The evaluation of diabetic neuropathy is associated with hyperglycemic responses, resulting in an alteration in various metabolic pathways, including protein kinase C pathway, polyol pathway and hexosamine pathway in Schwann and glial cells of neurons. The essential source of neuronal destruction is analogous to these respective metabolic pathways, thus identified as potential therapeutic targets. These pathways regulating therapeutic medications may be used for diabetic neuropathy, however, only target specific drugs could have partial therapeutic activity. Various antidiabetic medications have been approved and marketed, which possess the therapeutic ability to control hyperglycemia and ameliorate the prevalence of diabetic neuropathy. Among all antidiabetic medications, incretin therapy, including Glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors, are the most favorable medications for the management of diabetes mellitus and associated peripheral neuropathic complications. Besides enhancing glucose-evoked insulin release from pancreatic β-cells, these therapeutic agents also play a vital role to facilitate neurite outgrowth and nerve conduction velocity in dorsal root ganglion. Furthermore, incretin therapy also activates cAMP and ERK signalling pathways, resulting in nerve regeneration and repairing. These effects are evidently supported by a series of preclinical data and investigations associated with these medications. However, the literature lacks adequate clinical trial outcomes related to these novel antidiabetic medications. The manuscript emphasizes the pathogenesis, current pharmacological approaches and vivid description of preclinical and clinical data for the effective management of diabetic neuropathy.

Human interferon-stimulated gene 15 (ISG15) is a 15-kDa ubiquitin-like protein that can be detected as either free ISG15 or covalently associated with its target proteins through a process termed ISGylation. Interestingly, extracellular free ISG15 has been proposed as a cytokinelike protein, whereas ISGylation is a posttranslational modification. ISG15 is a small protein with implications in some biological processes and pathologies that include cancer. This review highlights the findings of both free ISG15 and protein ISGylation involved in several molecular pathways, emerging as central elements in some cancer types.

RNA helicase A (RHA) is a DExH-box helicase that plays regulatory roles in a variety of cellular processes, including transcription, translation, RNA splicing, editing, transport, and processing, microRNA genesis and maintenance of genomic stability. It is involved in virus replication, oncogenesis, and innate immune response. RHA can unwind nucleic acid duplex by nucleoside triphosphate hydrolysis. The insight into the molecular mechanism of helicase activity is fundamental to understanding the role of RHA in the cell. Herein, we reviewed the current advances on the helicase activity of RHA and its relevance to gene expression, particularly, to the genesis of circular RNA.

Neuropeptides are endogenous active substances that play important roles in a number of physiological processes and are ubiquitous in the nervous tissue in vivo. The gene encoding pedal peptide/orcokinin-type (PP/OK-type) neuropeptide is an important member of the neuropeptide gene family and is ubiquitous in invertebrates of Bilateria; orcokinin (OK) is mainly found in Arthropoda, while pedal peptide (PP) is mainly found in Mollusca. OK and PP are also present in other animals. PP/OK-type neuropeptides are a kind of multifunctional neuropeptides predominantly expressed in the nervous tissue and play important roles in the nerve regulation of movement. Moreover, OK has a number of other physiological functions. This review describes the distribution, expression, function and maturation of PP/OK-type neuropeptides to facilitate investigations of new functions and receptors of PP/OK-type neuropeptides, providing the theoretical foundation for the potential use of PP/OK-type neuropeptides in the prevention and control of agricultural and forestry pests, as an additive for skin care products and in the screening of drugs for the treatment of diabetes.

Chronic wound biofilm infections are a threat to the population with respect to morbidity and mortality. The presence of multidrug-resistant bacterial pathogens in chronic wound renders the action of antibiotics and antibiofilm agents difficult. Therefore an alternative therapy is essential for reducing bacterial biofilm burden. In this scenario, the peptide-based antibiofilm therapy for chronic wound biofilm management seeks more attention. A synthetic peptide with a broad range of antibiofilm activity against preformed and established biofilms, having the ability to kill multispecies bacteria within biofilms and possessing combinatorial activity with other antimicrobial agents, provides significant insights. In this review, we portray the possibilities and difficulties of peptide-mediated treatment in chronic wounds biofilm management and how it can be clinically translated into a product.

Salt stress is one of the major abiotic stresses that negatively affect crops worldwide. Plants have evolved a series of mechanisms to cope with the limitations imposed by salinity. Molecular mechanisms, including the upregulation of cation transporters such as the Na+/H+ antiporters, are one of the processes adopted by plants to survive in saline environments. NHX antiporters are involved in salt tolerance, development, cell expansion, growth performance and disease resistance of plants. They are integral membrane proteins belonging to the widely distributed CPA1 sub-group of monovalent cation/H⁺ antiporters and provide an important strategy for ionic homeostasis in plants under saline conditions. These antiporters are known to regulate the exchange of sodium and hydrogen ions across the membrane and are ubiquitous to all eukaryotic organisms. With the genomic approach, previous studies reported that a large number of proteins encoding Na⁺/H⁺ antiporter genes have been identified in many plant species and successfully introduced into desired species to create transgenic crops with enhanced tolerance to multiple stresses. In this review, we focus on plant antiporters and all the aspects from their structure, classification, function to their in silico analysis. On the other hand, we performed a genome-wide search to identify the predicted NHX genes in Argania spinosa L. We highlighted for the first time the presence of four putative NHX (AsNHX1-4) from the Argan tree genome, whose phylogenetic analysis revealed their classification in one distinct vacuolar cluster. The essential information of the four putative NHXs, such as gene structure, subcellular localization and transmembrane domains was analyzed.

Breast cancer is a heterogeneous malignancy and is the second leading cause of mortality among women around the world. Increasing the resistance to anti-cancer drugs in breast cancer cells persuades researchers to search the novel therapeutic approaches for the treatment of this malignancy. Among the novel methods, therapeutic peptides that target and disrupt tumor cells have been of great interest. Therapeutic peptides are short amino acid monomer chains with high specificity to bind and modulate a protein interaction of interest. Several advantages of peptides, such as specific binding on tumor cells surface, low molecular weight, and low toxicity on normal cells, make the peptides appealing therapeutic agents against solid tumors, particularly breast cancer. Also, the National Institutes of Health (NIH) describes therapeutic peptides as a suitable candidate for the treatment of drug-resistant breast cancer. In this review, we attempt to review the different therapeutic peptides against breast cancer cells that can be used in the treatment and diagnosis of the malignancy. Meanwhile, we presented an overview of peptide vaccines that have been developed for the treatment of breast cancer.