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Topic Review
Control of Protein Synthesis by ERdj1, ERdj2, ERdj6
The endoplasmic reticulum (ER) of mammalian cells is the central organelle for the maturation and folding of transmembrane proteins and for proteins destined to be secreted into the extracellular space. The proper folding of target proteins is achieved and supervised by a complex endogenous chaperone machinery. BiP, a member of the Hsp70 protein family, is the central chaperone in the ER. The chaperoning activity of BiP is assisted by ER-resident DnaJ (ERdj) proteins due to their ability to stimulate the low, intrinsic ATPase activity of BiP. Besides their co-chaperoning activity, ERdj proteins also regulate and tightly control the translation, translocation, and degradation of proteins. Three ERdj co-chaperones, ERdj1, ERdj2, and ERdj6, are functionally involved in the control of translation and translocation of ER target proteins. 
  • 705
  • 28 Jul 2022
Topic Review
Melanoma and The Ubiquitin Pathway
Ubiquitination is a post-translational modification that plays a crucial role in various cellular biological activities and participates in cancer pathogenesis, including melanoma. 
  • 430
  • 28 Jul 2022
Topic Review
MicroRNAs in Dystrophinopathy
Dystrophinopathies are a group of X-linked inheritance disorders characterized by loss of limbs, loss of respiratory and cardiac muscle strength, and destruction of nerve tissue. There are two main forms of dystrophinopathy: Duchenne muscular dystrophy (DMD), which develops in early childhood and presents with severe symptoms, and Becker muscular dystrophy (BMD), which develops late as a milder form.
  • 372
  • 28 Jul 2022
Topic Review
Secretory Immunoglobulin A Immunity in COPD
Chronic obstructive pulmonary disease (COPD), asthma and cystic fibrosis (CF) are distinct respiratory diseases that share features such as the obstruction of small airways and disease flare-ups that are called exacerbations and are often caused by infections. Along the airway epithelium, immunoglobulin (Ig) A contributes to first line mucosal protection against inhaled particles and pathogens. Dimeric IgA produced by mucosal plasma cells is transported towards the apical pole of airway epithelial cells by the polymeric Ig receptor (pIgR), where it is released as secretory IgA. Secretory IgA mediates immune exclusion and promotes the clearance of pathogens from the airway surface by inhibiting their adherence to the epithelium. 
  • 470
  • 27 Jul 2022
Topic Review
Application of Exfoliated Podocytes from Urine in CKD
Chronic kidney disease (CKD) is a global health issue, affecting more than 10% of the worldwide population. It is defined by structural and functional changes to the kidney. Urinary exfoliated podocytes and podocyte-specific markers have demonstrated value for the early diagnosis of CKD and prognosticating CKD progression.
  • 352
  • 27 Jul 2022
Topic Review
Heme Metabolism
Mitochondria are essential organelles of mammalian cells, often emphasized for their function in energy production, iron metabolism and apoptosis as well as heme synthesis. The heme is an iron-loaded porphyrin behaving as a prosthetic group by its interactions with a wide variety of proteins. These complexes are termed hemoproteins and are usually vital to the whole cell comportment, such as the proteins hemoglobin, myoglobin or cytochromes, but also enzymes such as catalase and peroxidases. The building block of porphyrins is the 5-aminolevulinic acid, whose exogenous administration is able to stimulate the entire heme biosynthesis route. In neoplastic cells, this methodology repeatedly demonstrated an accumulation of the ultimate heme precursor, the fluorescent protoporphyrin IX photosensitizer, rather than in healthy tissues.
  • 1.3K
  • 27 Jul 2022
Topic Review
The Sumoylation Pathway
Post-translational modifications (PTMs) are key regulators of most biological processes. Besides phosphorylation, methylation, acetylation and others, covalent modification of proteins by small polypeptides of the ubiquitin-like modifiers (UBLs) family have gained importance. Among UBLs, the small ubiquitin-like modifier (SUMO), of ~90 amino acids and discovered in the nineties, has proven to regulate most cellular processes. The sumoylation pathway is quite similar to the ubiquitination pathway, but there is its own set of enzymes for modification by SUMO.
  • 1.1K
  • 25 Jul 2022
Topic Review
Autophagy in Cell Survival and Cell Death
Autophagy is a process conserved from yeast to humans. Since the discovery of autophagy, its physiological role in cell survival and cell death has been intensively investigated. The inherent ability of the autophagy machinery to sequester, deliver, and degrade cytoplasmic components enables autophagy to participate in cell survival and cell death in multiple ways. The primary role of autophagy is to send cytoplasmic components to the vacuole or lysosomes for degradation. By fine-tuning autophagy, the cell regulates the removal and recycling of cytoplasmic components in response to various stress or signals. Autophagy also facilitates certain forms of regulated cell death. In addition, there is complex crosstalk between autophagy and regulated cell death pathways, with a number of genes shared between them, further suggesting a deeper connection between autophagy and cell death. Finally, the mitochondrion presents an example where the cell utilizes autophagy to strike a balance between cell survival and cell death.
  • 498
  • 22 Jul 2022
Topic Review
Drug Repositioning of PD-1/PD-L1 Checkpoint
Monoclonal antibodies targeting the PD-1/PD-L1 immune checkpoint have considerably improved the treatment of some cancers, but novel drugs, new combinations, and treatment modalities are needed to reinvigorate immunosurveillance in immune-refractory tumors. An option to elicit antitumor immunity against cancer consists of using approved and marketed drugs known for their capacity to modulate the expression and functioning of the PD-1/PD-L1 checkpoint. Specifically, the repositioning of the approved drugs liothyronine, azelnidipine (and related dihydropyridine calcium channel blockers), niclosamide, albendazole/flubendazole, and a few other modulators of the PD-1/PD-L1 checkpoint (repaglinide, pimozide, fenofibrate, lonazolac, propranolol) is presented. Their capacity to bind to PD-L1 or to repress its expression and function offer novel perspectives for combination with PD-1 targeted biotherapeutics. These known and affordable drugs could be useful to improve the therapy of cancer.
  • 525
  • 22 Jul 2022
Topic Review
Mitochondrial Unfolded Protein Response for Therapy
The mitochondrial unfolded protein response (UPRmt) is a mechanism aimed to preserve or repair damaged mitochondria. UPRmt is responsible for maintaining mitochondrial proteostasis via mitochondrial activation of a transcriptional program in the nuclear DNA. This compensation system can be divided into three main pathways: activation of (1) chaperones, which boost refolding of misfolded proteins to restore them to their functional conformation and assist the folding of newly synthesized proteins; (2) proteases that are able to degrade aberrant proteins or aggregates; and (3) an antioxidant system that palliates ROS overproduction. Although human UPRmt is not fully understood, it is gaining relevance in a variety of physiological processes on top of its canonical function, such as ageing, oxidative stress resistance, hematopoietic stem cell maintenance, glycolysis, antibacterial immunity, coenzyme Q biosynthesis, and mitochondrial fission. Loss of mitochondrial proteostasis is the main UPRmt inducer. Accumulation of damaged proteins exceeding the protein-processing capacity of the chaperones and proteases in mitochondria would activate UPRmt, for instance. Additionally, factors interfering with mitochondrial function promote UPRmt induction. Examples of these are the inhibition of complex I by rotenone, bacterial toxins, knockdown of quality control proteins, or generation of excess ROS by paraquat.
  • 405
  • 22 Jul 2022
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