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Topic Review
Presenilin-2
Presenilin-2 (PS2) is one of the three proteins that are dominantly mutated in familial Alzheimer’s disease (FAD). It forms the catalytic core of the γ-secretase complex—a function shared with its homolog presenilin-1 (PS1)—the enzyme ultimately responsible of amyloid-β  (Aβ) formation. PS2 is also involved in several functions, also independently of γ-secretase activity, ranging from Ca2+ signalling to inter-organelle communication and autophagy. FAD-linked PS2 mutations impact on multiple aspects of cell and tissue physiology, including bioenergetics and brain network excitability.
  • 959
  • 05 Nov 2020
Topic Review
Tetrahydrocurcumin-Related Neuropathic Protection
Tetrahydrocurcumin (THC) is a metabolite of curcumin (CUR). The benefits of THC may be associated with various mechanisms, including antinociceptive, anti-inflammatory, Ca2+-accumulation-inhibitive, TNF-α suppression, neuroprotective, and antioxidant activities.
  • 957
  • 15 May 2023
Topic Review
3,7-Dioleylquercetin
Quercetin is a well-known plant flavonol and antioxidant; however, there has been some debate regarding the efficacy and safety of native quercetin as a skin-whitening agent via tyrosinase inhibition. Several researchers have synthesized quercetin derivatives as low-toxicity antioxidants and whitening agents. However, no suitable quercetin derivatives have been reported to date. In this study, a novel quercetin derivative was synthesized by the SN2 reaction using quercetin and oleyl bromide. The relationship between the structures and activities of quercetin derivatives as anti-melanogenic agents was assessed using in vitro enzyme kinetics, molecular docking, and quenching studies; cell line experiments; and in vivo zebrafish model studies. Novel 3,7-dioleylquercetin (OQ) exhibited a low cytotoxic concentration level at >100 µg/mL (125 µM), which is five times less toxic than native quercetin.
  • 956
  • 06 May 2021
Topic Review
Purine-Metabolising Enzymes
The enzymes of both de novo and salvage pathways for purine nucleotide synthesis are regulated to meet the demand of nucleic acid precursors during proliferation. Among them, the salvage pathway enzymes seem to play the key role in replenishing the purine pool in dividing and tumour cells that require a greater amount of nucleotides. An imbalance in the purine pools is fundamental not only for preventing cell proliferation, but also, in many cases, to promote apoptosis. It is known that tumour cells harbour several mutations that might lead to defective apoptosis-inducing pathways, and this is probably at the basis of the initial expansion of the population of neoplastic cells. Therefore, knowledge of the molecular mechanisms that lead to apoptosis of tumoural cells is key to predicting the possible success of a drug treatment and planning more effective and focused therapies. 
  • 956
  • 29 Sep 2021
Topic Review
Biotechnologies in Perfume Manufacturing
The fragrance industry is increasingly turning to biotechnology to produce sustainable and high-quality fragrance ingredients. Microbial-based approaches have been found to be particularly promising, as they offer a more practical, economical and sustainable alternative to plant-based biotechnological methods for producing terpene derivatives of perfumery interest. Among the evaluated works, the heterologous expression of both terpene synthase and mevalonate pathway into Escherichia coli has shown the highest yields.
  • 956
  • 09 May 2023
Topic Review
Oxidative Stress-Mediated Inflammation in T2DM-Induced Diabetic Nephropathy
Diabetic nephropathy is manifested in more than 10% of people with diabetes. It is a common cause of kidney failure and end-stage kidney disease. Understanding of mechanisms underlying the initiation and development of diabetes-induced kidney injuries will allow for the development of more effective methods of prevention and treatment of the disease. Diabetic nephropathy is a wide-ranging complication of diabetes, and it is necessary to discuss the “weight” of pro-inflammatory pathways and molecules in the progress of renal injuries during the development of the disease. A large spectrum of pro-inflammatory molecules and pathways participate in different stages of the pathophysiological progression of diabetic nephropathy, including pro-inflammatory cytokines, chemokines, their receptors, adhesion molecules, and transcription factors. On the other hand, it is known that one of the consequences of hyperglycemia-induced ROS generation is the up-regulation of pro-inflammatory cascades, which, in turn, activate the transcription of genes encoding cytokines-chemokines, growth factors, and extracellular matrix proteins.
  • 955
  • 27 Dec 2022
Topic Review
ROS and Antioxidants in Halophytes
Reactive oxygen species (ROS) are excited or partially reduced forms of atmospheric oxygen, which are continuously produced during aerobic metabolism like many physiochemical processes operating throughout seed life. Previously, it was believed that ROS are merely cytotoxic molecules, however, now it has been established that they perform numerous beneficial functions in plants including many critical roles in seed physiology. ROS facilitate seed germination via cell wall loosening, endosperm weakening, signaling, and decreasing abscisic acid (ABA) levels. Most of the existing knowledge about ROS homeostasis and functions is based on the seeds of common plants or model ones.
  • 955
  • 30 Aug 2023
Topic Review
Computational Drug Design on Ion Channels
Ion channels play important roles in fundamental biological processes, such as electric signaling in cells, muscle contraction, hormone secretion, and regulation of the immune response. Targeting ion channels with drugs represents a treatment option for neurological and cardiovascular diseases, muscular degradation disorders, and pathologies related to disturbed pain sensation. While there are more than 300 different ion channels in the human organism, drugs have been developed only for some of them and available drugs lack selectivity. Computational approaches are an indispensable tool for drug discovery and can speed up, especially, the early development stages of lead identification and optimization. The number of molecular structures of ion channels has considerably increased over the last ten years, providing new opportunities for structure-based drug development.
  • 954
  • 09 Jun 2023
Topic Review
Role of SCAP/SREBP in Hepatic Steatosis
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a unique, multi-factorial condition with several phases of progression including steatosis, steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Sterol element binding protein 1c (SREBP1c) is the main transcription factor involved in regulating hepatic de novo lipogenesis. This transcription factor is synthesized as an inactive precursor, and its proteolytic maturation is initiated in the membrane of the endoplasmic reticulum upon stimulation by insulin. SREBP cleavage activating protein (SCAP) is required as a chaperon protein to escort SREBP from the endoplasmic reticulum and to facilitate the proteolytic release of the N-terminal domain of SREBP into the Golgi. SCAP inhibition prevents activation of SREBP and inhibits the expression of genes involved in triglyceride and fatty acid synthesis, resulting in the inhibition of de novo lipogenesis.
  • 954
  • 24 Jan 2024
Topic Review
GM1 Ganglioside and Parkinson’s Disease
GM1 (monosialotetrahexosylganglioside) the "prototype" ganglioside, is a member of the ganglio series of gangliosides which contain one sialic acid residue. GM1 has important physiological properties and impacts neuronal plasticity and repair mechanisms, and the release of neurotrophins in the brain.
  • 954
  • 18 Feb 2022
Topic Review
Tumor-Infiltrating Lymphocytes and PD-L1-Positive Cells
This review discusses two topics: (i) the prognostic impact of tumor-infiltrating lymphocytes and (ii) predictive biomarkers for immune checkpoint inhibitors, to shed light on lymphocyte migration in four solid tumors, the urothelial carcinoma, renal cell carcinoma, prostate cancer, and retroperitoneal sarcoma.
  • 953
  • 19 Nov 2020
Topic Review
Anticancer Effects of Glyceollins
Glyceollins are a group of phytoalexins that are isolated from soybeans. They have attracted attention because they exert numerous effects on human functions and diseases, notably anticancer effects.
  • 952
  • 28 Oct 2021
Topic Review
Molecular Interactions in the Diabetic Brain
Diabetes mellitus (DM) has been associated with cognitive complications in the brain resulting from acute and chronic metabolic disturbances happening peripherally and centrally. Numerous studies have reported on the morphological, electrophysiological, biochemical, and cognitive changes in the brains of diabetic individuals. The detailed pathophysiological mechanisms implicated in the development of the diabetic cognitive phenotype remain unclear due to intricate molecular changes evolving over time and space. This study provides an insight into recent advances in understanding molecular events in the diabetic brain, focusing on cerebral glucose and insulin uptake, insulin action in the brain, and the role of the brain in the regulation of glucose homeostasis. Fully competent mitochondria are essential for energy metabolism and proper brain function; hence, the potential contribution of mitochondria to the DM-induced impairment of the brain is also discussed. 
  • 952
  • 18 Jan 2022
Topic Review
Cysteinyl Leukotrienes as Multifunctional Inflammation Mediators
Montelukast (MTK)—an antagonist of the cysteinyl leukotrienes receptor 1—is widely used in the management of symptoms among adults and children. Initially described as the slow-reacting substances of anaphylaxis, leukotrienes (LTs) are pro-inflammatory lipid mediators derived from arachidonic acid. Its systemic anti-inflammatory actions, which are particularly important in the brain tissues, are at the onset of various clinical studies focused on the repurposing of this drug for various other diseases, aimed particularly at Alzheimer’s and Parkinson’s diseases.
  • 951
  • 21 Sep 2022
Topic Review
Diverse Downstream Effectors of RRAD
Ras-related associated with diabetes (RRAD), a member of the Ras-related GTPase superfamily, is primarily a cytosolic protein that actives in the plasma membrane. RRAD is highly expressed in type 2 diabetes patients and as a biomarker of congestive heart failure. Mounting evidence showed that RRAD is important for the progression and metastasis of tumor cells, which play opposite roles as an oncogene or tumor suppressor gene depending on cancer and cell type. 
  • 951
  • 11 Apr 2023
Topic Review
PTMs and Mutations of Human Linker Histone Subtypes
Linker histones (LH) are a critical component of chromatin in addition to the canonical histones (H2A, H2B, H3, and H4). In humans, 11 subtypes (7 somatic and 4 germinal) of linker histones have been identified, and their diverse cellular functions in chromatin structure, DNA replication, DNA repair, transcription, and apoptosis have been explored, especially for the somatic subtypes. Delineating the unique role of human linker histone (hLH) and their subtypes is highly tedious given their high homology and overlapping expression patterns. However, advancements in mass spectrometry combined with HPLC have helped in identifying the post-translational modifications (PTMs) found on the different LH subtypes. However, while a number of PTMs have been identified and their potential nuclear and non-nuclear functions explored in cellular processes, there are very few studies delineating the direct relevance of these PTMs in diseases. In addition, whole-genome sequencing of clinical samples from cancer patients and individuals afflicted with Rahman syndrome have identified high-frequency mutations and therefore broadened the perspective of the linker histone mutations in diseases.
  • 950
  • 19 Jan 2023
Topic Review
Hydrogen Sulfide in Mammalian Cells
Hydrogen sulfide (H2S) was recognized as a gaseous signaling molecule, similar to nitric oxide (-NO) and carbon monoxide (CO). It's important to provide an overview of the formation of hydrogen sulfide (H2S) in the human body. H2S is synthesized by enzymatic processes involving cysteine and several enzymes, including cystathionine-β-synthase (CBS), cystathionine-γ-lyase (CSE), cysteine aminotransferase (CAT), 3-mercaptopyruvate sulfurtransferase (3MST) and D-amino acid oxidase (DAO). The physiological and pathological effects of hydrogen sulfide (H2S) on various systems in the human body have led to extensive research efforts to develop appropriate methods to deliver H2S under conditions that mimic physiological settings and respond to various stimuli. These functions span a wide spectrum, ranging from effects on the endocrine system and cellular lifespan to protection of liver and kidney function. The exact physiological and hazardous thresholds of hydrogen sulfide (H2S) in the human body are currently not well understood and need to be researched in depth. 
  • 950
  • 18 Dec 2023
Topic Review
Application of Proteomics in Giardia duodenalis
Giardia duodenalis remains a neglected tropical disease. A key feature of the sustained transmission of Giardia is the ability to form environmentally resistant cysts. Valuable information from proteomics analyses of G. duodenalis has been discovered in terms of the pathogenesis and virulence of Giardia, which may provide guidance for the development of better means with which to prevent and reduce the impacts of giardiasis.
  • 949
  • 18 Nov 2022
Topic Review
Role of Yes-Associated Protein in Breast Cancer
The hippo/yes-associated protein (YAP) protein is a critical oncogenic mediator within the Hippo signaling pathway and has been implicated in various cancer types. In breast cancer, it frequently becomes activated, thereby contributing to developing drug-resistance mechanisms. Studies have underscored the intricate interplay between YAP and ferroptosis within the breast tumor microenvironment. YAP exerts a negative regulatory effect on ferroptosis, promoting cancer cell survival and drug resistance.
  • 948
  • 17 Jan 2024
Topic Review
Mitochondrial Redox Metabolism
Mitochondrial redox metabolism is the central component in the cellular metabolic landscape, where anabolic and catabolic pathways are reprogrammed to maintain optimum redox homeostasis. During different stages of cancer, the mitochondrial redox status plays an active role in navigating cancer cells’ progression and regulating metabolic adaptation according to the constraints of each stage. Mitochondrial reactive oxygen species (ROS) accumulation induces malignant transformation. Once vigorous cell proliferation renders the core of the solid tumor hypoxic, the mitochondrial electron transport chain mediates ROS signaling for bringing about cellular adaptation to hypoxia. Highly aggressive cells are selected in this process, which are capable of progressing through the enhanced oxidative stress encountered during different stages of metastasis for distant colonization. Mitochondrial oxidative metabolism is suppressed to lower ROS generation, and the overall cellular metabolism is reprogrammed to maintain the optimum NADPH level in the mitochondria required for redox homeostasis. After reaching the distant organ, the intrinsic metabolic limitations of that organ dictate the success of colonization and flexibility of the mitochondrial metabolism of cancer cells plays a pivotal role in their adaptation to the new environment.
  • 946
  • 24 Nov 2021
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