Role of Tau in Various Tauopathies, Treatment Approaches, and Emerging Role of Nanotechnology in Neurodegenerative Disorders.

A few protein kinases and phosphatases regulate tau protein phosphorylation and an imbalance in their enzyme activity results in tau hyper-phosphorylation. Aberrant tau phosphorylation causes tau to dissociate from the microtubules and clump together in the cytosol to form neurofibrillary tangles (NFTs), which lead to the progression of neurodegenerative disorders including Alzheimer's disease (AD) and other tauopathies. Hence, targeting hyperphosphorylated tau protein is a restorative approach for treating neurodegenerative tauopathies. The cyclin-dependent kinase (Cdk5) and the glycogen synthase kinase (GSK3ß) have both been implicated in aberrant tau hyperphosphorylation. The limited transport of drugs through the blood-brain barrier (BBB) for reaching the central nervous system (CNS) thus represents a significant problem in the development of drugs. Drug delivery systems based on nanocarriers help solve this problem. In this review, we discuss the tau protein, regulation of tau phosphorylation and abnormal hyperphosphorylation, drugs in use or under clinical trials, and treatment strategies for tauopathies based on the critical role of tau hyperphosphorylation in the pathogenesis of the disease. Pathology of neurodegenerative disease due to hyperphosphorylation and various therapeutic approaches including nanotechnology for its treatment.

Highlighting the Potential Role of Exosomes as the Targeted Nanotherapeutic Carrier in Metastatic Breast Cancer.

Breast cancer, being the second most common type of cancer, is a leading cause of death in the female population. Of all the available treatments existing for breast cancer, exosomes appear as an important medium for the site targeted delivery of the drugs. Exosomes, unlike all the other extracellular vesicles, play a vital role in the transport of numerous biomolecules throughout the body and can easily be detected because of the presence of specific biomarkers. Apart from playing a wide variety of roles in the progression of many diseases, they are also responsible for tumor progression and metastasis in breast cancer. Exosomes and related engineering strategies are being discussed as nano-carrier for the delivery of different drugs in the case of breast cancer. Overall, we have discussed in this review the role of exosomes in breast cancer and the engineering strategies being devised for making them an efficient drug delivery system.

Organic quantum dots: An ultrasmall nanoplatform for cancer theranostics.

Tumours are the second leading cause of death globally, generating alterations in biological interactions and, as a result, malfunctioning of crucial genetic traits. Technological advancements have made it possible to identify tumours at the cellular level, making transcriptional gene variations and other genetic variables more easily investigated. Standard chemotherapy is seen as a non-specific treatment that has the potential to destroy healthy cells while also causing systemic toxicity in individuals. As a result, developing new technologies has become a pressing necessity. QDs are semiconductor particles with diameters ranging from 2 to 10 nanometers. QDs have grabbed the interest of many researchers due to their unique characteristics, including compact size, large surface area, surface charges, and precise targeting. QD-based drug carriers are well known among the many nanocarriers. Using QDs as a delivery approach enhances solubility, lengthens retention time, and reduces the harmful effects of loaded medicines. Several varieties of quantum dots used in drug administration are discussed in this article, along with their chemical and physical characteristics and manufacturing methods. Furthermore, it discusses the role of QDs in biological, medicinal, and theranostic applications.

Peptide Utility (PU) search server: A new tool for peptide sequence search from multiple databases.

Proteins are essential building blocks in humans that have garnered huge attention from researchers worldwide due to their numerous therapeutic applications. To date, different computational tools have been developed to extract pre-existing information on these biological molecules, but most of these tools suffer from limitations such as non-user friendly interface, redundancy of data, etc. To overcome these limitations, a user-friendly interface, the Peptide Utility (PU) webserver (https://chain-searching.herokuapp.com/) has been developed for searching and analyzing homologous and identical protein/peptide sequences that can be searched from approximately 0.4 million sequences (structural and sequence information) in both online and offline modes. The PU web server can also be used to study different types of interactions in PDBSum, identifying the most dominating interface residues, the most prevalent interactions, and the interaction preferences of different residues. The webserver would also pave way for the design of novel therapeutic peptides and folds by identifying conserved residues in the three-dimensional structure space of proteins.

Overexpression of Endogenous Anti-Oxidants with Selenium Supplementation Protects Trophoblast Cells from Reactive Oxygen Species-Induced Apoptosis in a Bcl-2-Dependent Manner.

The human placenta provides life support for the developing foetus, and a healthy placenta is a prerequisite to a healthy start to life. Placental tissue is subject to oxidative stress which can lead to pathological conditions of pregnancy such as preeclampsia, preterm labour and intrauterine growth restriction. Up-regulation of endogenous anti-oxidants may alleviate placental oxidative stress and provide a therapy for these complications of pregnancy. In this study, selenium supplementation, as inorganic sodium selenite (NaSel) or organic selenomethionine (SeMet), was used to increase the protein production and cellular activity of the important redox active proteins glutathione peroxidase (GPx) and thioredoxin reductase (Thx-Red). Placental trophoblast cell lines, BeWo, JEG-3 and Swan-71, were cultured in various concentrations of NaSel or SeMet for 24 h and cell extracts prepared for western blots and enzyme assays. Rotenone and antimycin were used to stimulate mitochondrial reactive oxygen species (ROS) production and induce apoptosis. Trophoblast cells supplemented with 100 nM NaSel and 500 nM SeMet exhibited significantly enhanced expression and activity of both GPx and Thx-Red. Antimycin and rotenone were found to generate ROS when measured by 2',7'-dichlorofluorescein diacetate (DCFDA) assay, and selenium supplementation was shown to reduce ROS production in a dose-dependent manner. Rotenone, 100 µM treatment for 4 h, caused trophoblast cell apoptosis as evidenced by increased Annexin V binding and decreased expression of Bcl-2. In both assays of apoptosis, selenium supplementation was able to prevent apoptosis, preserve Bcl-2 expression and protect trophoblast cells from mitochondrial oxidative stress. This data suggests that selenoproteins such as GPx and Thx-Red have an important role in protecting trophoblast cells from mitochondrial oxidative stress and that selenium supplementation may be important in treating some placental pathologies.

Selenium supplementation induces mitochondrial biogenesis in trophoblasts.

INTRODUCTION: Placental oxidative stress has been implicated in pregnancy complications and previous work has shown that selenium can protect trophoblast mitochondria from oxidative stress. This report examines mitochondrial function and content in trophoblasts supplemented with selenium. METHODS: Swan-71, JEG-3 and BeWo cells and placental tissue were incubated with sodium selenite or selenomethionine. Mitochondrial function was examined in a respirometer. Mitochondrial content was determined using RT-PCR. The levels of the mitochondrial biogenesis markers selenoprotein H, PGC-1α and NRF-1 was examined by western blotting. RESULTS: Mitochondrial respiration was significantly enhanced post selenium supplementation in cells and tissues. Selenium supplementation increased mitochondrial content and up-regulated mitochondrial biogenesis mediators in cells. DISCUSSION: These results emphasise the importance of selenium in mitochondrial regeneration in trophoblasts.