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Topic Review
Protein-Based Targeting Self-Assembling Nanoparticles for Biomedical Applications
Targeted nanoparticles of different origins are considered as new-generation diagnostic and therapeutic tools. Targeted protein self-assembling nanoparticles circumvent this problem since proteins are encoded in DNA and the final protein product is produced in only one possible way. The combination of the endless biomedical potential of protein carriers as nanoparticles and the standardized protein purification protocols will make significant progress in “magic bullet” creation possible, bringing modern biomedicine to a new level. The entry focused on the currently existing platforms for targeted self-assembling protein nanoparticles based on transferrin, lactoferrin, casein, lumazine synthase, albumin, ferritin, and encapsulin proteins, as well as on proteins from magnetosomes and virus-like particles. The applications of these self-assembling proteins for targeted delivery in vitro and in vivo are thoroughly discussed, including bioimaging applications and different therapeutic approaches, such as chemotherapy, gene delivery, and photodynamic and photothermal therapy. 
  • 1.8K
  • 08 Mar 2023
Topic Review
Astrocyte Pathology in Neurodevelopmental Disorders
The discovery in the last decade of unique astroglial features that include their role in synaptic plasticity and memory function has broadened and refurbished the conception of brain function in health and disease. Astrocytes are both necessary and sufficient for memory function, and contribute to the pathophysiology of cognitive and intellectual disability disorders such as Alzheimer’s disease, Fragile X syndrome (FXS), or Down syndrome (DS). We review some of the most relevant studies demonstrating that astrocytes are involved in the synaptic pathology of the two most common genetic forms of intellectual disability (FXS and DS).
  • 1.8K
  • 11 Dec 2020
Topic Review
Protein Glutathionylation and Glutaredoxin in Neurodegenerative Diseases
The brain is highly sensitive to oxidative stress due to its high oxygen consumption, abundance of unsaturated fatty acids which are prone to oxidation, and low antioxidant levels. It is a metabolically active and a high energy demanding organ that relies heavily on mitochondria for its energy needs. Majority of oxygen consumed by mitochondria during oxidative phosphorylation is coupled to ATP synthesis while ~4% contributes to the generation of superoxides which are further metabolized to reactive oxygen species (ROS). ROS modify proteins causing functional and structural damage to biomolecules. Prolonged exposure to reactive oxygen species (ROS) also damages DNA, mitochondrial membranes, and lipids, impairing its metabolic functions including synthesis of ATP, fatty acid oxidation and metabolism of essential biomolecules.
  • 1.8K
  • 16 Dec 2022
Topic Review
Histone Acetyltransferase GCN5
Transcription of protein-encoding genes starts with forming a pre-initiation complex comprised of RNA polymerase II and several general transcription factors. To activate gene expression, transcription factors must overcome the repressive chromatin structure, which is accomplished with multiprotein complexes. Histone Acetyl Transferases (HAT) catalyze acetylation of specific lysine residues in histone N-tails, which are involved in transcriptional regulation and other nuclear processes. HATs are parts of large multiprotein complexes, like the SAGA complex, where their activity is enhanced, and their substrate specificity is altered. The whole complex is recruited to target sequences on the genome with other components involved in protein-protein interactions. A prototypical HAT which acts as a transcriptional adaptor is known as General Control Nonrepressed protein 5 (GCN5), first identified in Saccharomyces cerevisiae. GCN5 was defined biochemically as the first transcription-linked HAT with specificity for histone H3 lysine 14 (H3K14). However, GCN5 could also acetylate additional histone lysine residues, such as H3K9, H3K18, H3K23, H3K27, H3K36, other histones such as H4 and H2B and non-histone nuclear proteins.  In Arabidopsis, GCN5 is required for many developmental processes such as leaf development, apical dominance, root meristem activity, inflorescence, floral meristem function and flower fertility. 
  • 1.8K
  • 10 Feb 2021
Topic Review
ANO1 in Cystic Fibrosis
Cystic fibrosis (CF) is the most common of rare hereditary diseases in Caucasians, and it is estimated to affect 75,000 patients globally. CF is a complex disease due to the multiplicity of mutations found in the CF transmembrane conductance regulator (CFTR) gene causing the CFTR protein to become dysfunctional. Although CFTR is the main chloride channel in the lungs, others could, e.g., anoctamin-1 (ANO1 or TMEM16A), compensate for the deficiency of CFTR. 
  • 1.8K
  • 26 Oct 2021
Topic Review
Cell Membrane Theory of Senescence
Lipids are an essential constituent of the cell membrane of which polyunsaturated fatty acids (PUFAs) are the most important component. Activation of phospholipase A2 (PLA2) induces the release of PUFAs from the cell membrane that form precursors to both pro- and ant-inflammatory bioactive lipids that participate in several cellular processes. PUFAs GLA (gamma-linolenic acid), DGLA (dihomo-GLA), AA (arachidonic acid), EPA (eicosapentaenoic acid) and DHA (do-cosahexaenoic acid) are derived from dietary linoleic acid (LA) and alpha-linolenic acid (ALA) by the action of desaturases whose activity declines with age. Consequently, aged cells are deficient in GLA, DGLA, AA, AA, EPA and DHA and their metabolites. LA, ALA, AA, EPA and DHA can also be obtained direct from diet and their deficiency (fatty acids) may indicate malnutrition and deficiency of several minerals, trace elements and vitamins some of which are also much needed co-factors for the normal activity of desaturases. In many instances (patients) the plasma and tissue levels of GLA, DGLA, AA, EPA and DHA are low (as seen in patients with hyperten-sion, type 2 diabetes mellitus) but they do not have deficiency of other nutrients. Hence, it is reasonable to consider that the deficiency of GLA, DGLA, AA, EPA and DHA noted in these condi-tions are due to the decreased activity of desaturases and elongases. PUFAs stimulate SIRT1 through protein kinase A-dependent activation of SIRT1-PGC1α complex and thus, increase rates of fatty acid oxidation and prevent lipid dysregulation associated with aging. 
  • 1.8K
  • 19 Mar 2021
Topic Review
Glycosylation
Post-translational modifications are one way that biomineral-associated cells control the function and fate of proteins. Of the ten different types of post-translational modifications, one of the most interesting and complex is glycosylation, or the covalent attachment of carbohydrates to amino acid sidechains Asn, Ser, and Thr of proteins. There are several biomineral-associated glycoproteins that have been characterized, and a subset of these have been the subject of intensive in vitro experimentation.  These studies indicate that glycosylation does not alter the inherent function of the biomineralization protein; rather, it either accentuates or attenuates protein functionality. In essence, glycosylation gives the cell the “last word” as to what degree a biomineralization protein will participate in the biomineralization process.
  • 1.8K
  • 25 Sep 2020
Topic Review
Lipid Phosphate Phosphatases
Lipid phosphate phosphatases (LPPs) consist of three enzymes (LPP1–3), which have been classified as phospholipid phosphatases (PLPP). The LPPs dephosphorylate a wide spectrum of bioactive lipid phosphates, among which lysophosphatidate (LPA) and sphingosine 1-phosphate (S1P) are two important extracellular signaling molecules. The LPPs are integral membrane proteins, which are partly localized on plasma membranes. These activities participate in regulating the concentrations of extracellular LPA and S1P and thus signaling through their families of G protein coupled receptors. The expression of the LPPs on intracellular membranes, including endoplasmic reticulum and Golgi net work, are thought to attenuate signaling downstream of the activation of LPA and protease activates receptors. The LPPs differentially regulate signal transduction in cancer cells. LPP1 and LPP3 have decreased expressions in several caners and this is associated with increased tumor growth and metastasis.  Conversely, LPP2 activity is increased in these cancers and this accelerates progression through the cell cycle. Increasing the relative activities of LPP1 and LPP3 and decreasing LPP2 activity, therefore, provides a novel approach to treating some cancers.
  • 1.8K
  • 11 Sep 2020
Topic Review
The Keap1–Nrf2 Pathway
The Nrf2 is a transcription factor and it belongs to cap ‘n’ collar (CNC) basic leucine zipper (bZIP) protein subfamilies.
  • 1.8K
  • 23 Dec 2020
Topic Review
Curcumin in Chronic Hepatitis
Curcumin, as a natural product, is inexpensive, without side effects, and can stimulate very well certain areas of the human immune system. The cytotoxicity of curcumin as photosensitizer could be expanded by the intravenous blue laser blood irradiation (IVBLBI) or photobiomodulation in patients with chronic hepatitis B infection, Hepatitis B e-antigen (HBeAg)-positive, noncirrhotic, but nonresponsive to classical therapy. 
  • 1.8K
  • 26 May 2021
Topic Review
G Protein-Coupled Receptor with the Aging-Related Mechanisms
G protein-coupled receptors (GPCRs) represent one of the most functionally diverse classes of transmembrane proteins. GPCRs and their associated signaling systems have been linked to nearly every physiological, and also pathophysiological, process. G protein-coupled receptor 19 (GPR19), is a novel orphan GPCR that likely represents an important new target for novel remedial strategies for pathological disease conditions associated with aging-related cellular and tissue damage.
  • 1.8K
  • 16 Nov 2022
Topic Review
High-Value Bioactive Primary Metabolites of Microalgae
Microalgae is an aquatic microorganism with a plethora of diverse bioactive compounds including phenolics, carotenoids, vitamin B12 and peptides. Microalgal bioactive compounds have been shown to possess positive health effects such as antihypertensive, anti-obesity, antioxidative, anticancer and cardiovascular protection.
  • 1.8K
  • 08 Jul 2023
Topic Review
Cytochrome P450 in Escherichia coli
Cytochrome P450 (CYP) enzymes play important roles in metabolising endogenous and xenobiotic substances. Characterisations of human CYP proteins have been advanced with the rapid development of molecular technology that allows heterologous expression of human CYPs. Among several hosts, bacteria systems such as Escherichia coli (E. coli) have been widely used thanks to their ease of use, high level of protein yields, and affordable maintenance costs.
  • 1.8K
  • 23 Feb 2023
Topic Review
Toll-Like Receptor 4
Toll-like receptors (TLRs) are type I transmembrane glycoproteins belonging to the complex pattern recognition receptors (PRRs) expressed in immune and non-immune cells, including neurons and glia, which are involved in the regulation of innate immune and inflammatory responses. The TLR family comprises 11 members (TLR1–TLR11) in human and 12 (TLR1–TLR9, TLR11–TLR13) in mouse. TLR4 is one of the best characterized TLRs that surveys for the presence of structural motifs in a wide array of invading microorganisms, named pathogen-associated molecular patterns (PAMPs), and endogenous damage or danger molecular patterns (DAMPs), also known as alarmins, released by damaged cells and injured tissues or derived from apoptotic and necrotic cells. Activation of TLR4 induces the downstream start of inflammasome pathways which results in the release of a plethora of pro-inflammatory cytokines, Type I interferons (IFNs) and other inflammatory mediators.
  • 1.8K
  • 28 Mar 2023
Topic Review
AB5 Derivatives of Cyclotriphosphazene
AB5 compounds issued from the reactivity of hexachlorocyclotriphosphazene are relatively easy to obtain using two ways: either first the reaction of one chloride with one reagent, followed by the reaction of the five remaining Cl with another reagent, or first the reaction of five chlorides with one reagent, followed by the reaction of the single remaining Cl with another reagent. This particular property led to the use of such compounds as core for the synthesis of dendrons (dendritic wedges), using the five functions for growing the dendritic branches. The single function can be used for the synthesis of diverse types of dendrimers (onion peel, dumbbell-shape, Janus), for covalent or non-covalent grafting to solid surfaces, providing nanomaterials, for grafting a fluorophore, especially for studying biological mechanisms, or for self-associations to get micelles.
  • 1.8K
  • 04 Aug 2021
Topic Review
Genetically Encoded Fluorescent Redox Biosensors
In the most general sense of this term, a genetically encoded fluorescent redox biosensor is a kind of genetic system that changes a fluorescence in response to a redox event. Most often, such a tool is a chimeric protein consisting of a sensory domain that responds to a redox stimulus, and a domain whose fluorescence changes depending on alterations occurring with the sensory domain. It can also be a single-domain fluorescent protein, the structure of which changes when exposed to a redox stimulus, and the change in the structure leads to a change in fluorescence. In addition, there are transcriptional reporters, the principle of which is based on the alteration of the transcription of the fluorescent protein gene upon exposure to a redox stimulus. This article will focus on protein genetically encoded fluorescent redox biosensors that are currently used in in vivo research.
  • 1.8K
  • 11 Dec 2020
Topic Review
Effect of Metals in Transthyretin
Transthyretin (TTR) is a plasma homotetrameric protein that transports thyroxine and retinol. TTR itself, under pathological conditions, dissociates into partially unfolded monomers that aggregate and form fibrils. Metal ions such as Zn2+, Cu2+, Fe2+, Mn2+ and Ca2+ play a controversial role in the TTR amyloidogenic pathway. TTR is also present in cerebrospinal fluid (CSF), where it behaves as one of the major Aβ-binding-proteins. The interaction between TTR and Aβ is stronger in the presence of high concentrations of Cu2+. Crystals of TTR, soaked in solutions of physiological metals such as Cu2+ and Fe2+, but not Mn2+, Zn2+, Fe3+, Al3+, Ni2+, revealed an unusual conformational change. 
  • 1.8K
  • 25 Apr 2021
Topic Review
Calprotectin As a Drug Target
Calprotectin (CP), a heterodimer of S100A8 and S100A9 EF-hand calcium-binding proteins, is an integral part of the innate immune response. CP exploits the metal requirement of pathogens in the host immune response through the chelation of transition metals, starving pathogens of these nutrients. In addition, CP plays a role in the inflammatory response by acting as a ligand for cell surface receptors that signal through the NF-κB signaling pathway.
  • 1.8K
  • 21 Apr 2022
Topic Review
Therapeutic Potential of G-quadruplex Structural Junctions
We analyze further extension of G-quadruplexes by additional structural elements and investigate whether junction of G-quadruplex with duplex, hairpin, triplex or second G-quadruplex motif is favorable for aptamers stability and biological activity. Furthermore, we indicate the specific and pivotal role of G-quadruplex domain and the additional structural elements in the interactions with target molecules. Finally, we consider the potency of G-quadruplex junctions in the future applications and indicate the emerging research area that is still waiting for development to obtain highly specific and effective nucleic acid-based molecular tools.
  • 1.8K
  • 15 Oct 2021
Topic Review
Glutamate Receptor in Alzheimer’s and Parkinson’s Diseases
Glutamate excitotoxicity is a complex biological process that initiates when glutamate receptors are activated, leading to damage in dendrites and eventually causing cell death.
  • 1.8K
  • 13 Nov 2023
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