Diseases of the Nervous System
George Feuer, Felix A. de la Iglesia in Molecular Biochemistry of Human Disease, 2020
Many biochemical changes are found in children with Down’s disease. These abnormalities are quantitative rather than qualitative. In this disorder, the defective homeostasis is aggravated by the chromosomal anomaly. Serum proteins show some defects, which are age dependent to some extent. Essentially, total serum protein levels are normal, α- and γ- globulins are increased, and albumin is decreased. Abnormalities of protein transport across cell membranes can cause these changes. There are differences in peptide patterns from identical serum-globulin fractions between normal individuals and patients with Down’s disease. Serum calcium is reduced and urinary calcium excretion is low. However, serum phosphate levels are essentially normal, and there is defective transport of fat soluble vitamins. The reduced calcium level is in connection with defects of the skeletal and nervous system found in Down’s disease and may be associated with the deficiency in the absorption, transport, and utilization of vitamin D. Insufficient parathyroid activity may also be related to the altered calcium metabolism.
The YPT Protein Family in Yeast
Juan Carlos Lacal, Frank McCormick in The ras Superfamily of GTPases, 2017
Six genes encoding Ypt proteins have been identified thus far in baker’s yeast (Figure 2). A link between Ypt proteins and intracellular transport processes became evident from observations showing that mutants of the most intensively studied genes, YPT1 and SEC4, accumulate membrane-enclosed structures of the secretion machinery, i.e., ER and Golgi-derived vesicular intermediates,4,13,14 and are defective in the passage of proteins through different compartments of the secretory pathway. As outlined below, preliminary studies show that other, recently identified Ypt proteins in S. cerevisiae are likely to also act as regulators in the endocytic pathway. Clearly, the maintenance of the organelles involved in protein transport is a dynamic process that requires a constant balance of incoming and outgoing membranes (vesicles) and there must be membrane-associated and/or membrane-spanning factors that are responsible for establishing the identity of each organelle uniquely. Likewise, the targeting of vesicles must be carefully controlled, so that incoming vesicles recognize the proper acceptor membrane, successfully dock, and fuse. Finally, there must be processes that maintain an equilibrium between incoming and outgoing vesicles, most probably a recycling mechanism that scavenges received membrane material (from the vesicles) and sends it back to a donor organelle. It is these membrane transport processes where small guanine nucleotide-binding proteins of the Ypt/Rab family seem to play a key regulatory role in all eukaryotic cells.
The microcirculation and solute exchange
Neil Herring, David J. Paterson in Levick's Introduction to Cardiovascular Physiology, 2018
Nevertheless, vesicular transport may contribute significantly to macromolecular transfer at low filtration rates. Macromolecules such as gold-labelled albumin and ferritin (radius: 5.5 nm) undoubtedly enter the luminal caveo- lae and appear soon afterwards in the abluminal caveolae (Figures 9.5 and 9.6). However, it remains unclear how much this contributes to total protein transport. It is possible that, at normal, low capillary filtration rates, conductive channels and vesicular transport both contribute to protein permeation.
Modifying antibody-FcRn interactions to increase the transport of antibodies through the blood-brain barrier
Published in mAbs, 2023
Jason Tien, Dmitri Leonoudakis, Ralitsa Petrova, Vivian Trinh, Tetsuya Taura, Debapriya Sengupta, Lisa Jo, Angela Sho, Yong Yun, Eric Doan, Anita Jamin, Hussein Hallak, David S. Wilson, Jennifer R. Stratton
Protein transport across the BBB can occur via several different pathways broadly divided into paracellular and transcellular mechanisms.42 Since RMT is a transcellular process, we reasoned that it can only occur if an antibody protein is internalized by brain endothelial cells. We therefore established an antibody internalization assay based on previous work43 to investigate whether O4-YTE hIgG1 transport is accompanied by cellular internalization of the antibody. Since other groups have noted that FcRn-mediated transport is best studied in systems that overexpress both the FcRn heavy chain and β2-microglobulin (β2 M),44–46 we generated a stable HEK293 cell line expressing mouse FcRn and mouse β2 M. In this assay, antibodies were first incubated with cells for up to 4.25 h, after which unbound antibodies were washed off and the cells fixed. Extracellular antibodies were then blocked with unlabeled anti-human Fab, and the cells were washed and fixed again. Finally, cells were permeabilized and stained with anti-human IgG fluorescent conjugates to reveal only intracellularly stained antibodies (see methods for more details).
Effects of 4-phenylbutyric acid on the development of diabetic retinopathy in diabetic rats: regulation of endoplasmic reticulum stress-oxidative activation
Published in Archives of Physiology and Biochemistry, 2023
Amany Abdel-Ghaffar, Ghada G. Elhossary, Atef M. Mahmoud, Amany H. M. Elshazly, Olfat A. Hassanin, Anisa Saleh, Sahar M. Mansour, Fatma G. Metwally, Laila K. Hanafy, Sawsan H. Karam, Neveen Darweesh, Ahmed Mostafa Ata
The main ER stress defence strategy of the cell is up-regulation of the chaperone capacity. In cellular homeostasis, chaperones, as specialised proteins, play a key role. They assist in many cellular processes such as cellular signalling, assembly of the macromolecular complexes, protein folding, and protein transport (Ullman et al.2008). Chaperones’ main function in the ER is to protect against undesirable aggregation of nascent peptide chains while protein synthesis and to direct them towards folding, transport, or degradation pathways. In the unstressed cell, chaperones are expressed and maintained at steady levels but in the condition of stress, they are expressed in a perfectly regulated manner. Upon deregulation of chaperone activity, the misfolded aggregated or unfolded proteins are either targeted to accumulate in cells or to degradation pathways with the result of impairment in function and risk of generation of different pathogenesis (Engin and Hotamisligil 2010). Additionally, chaperones can act as signal transduction molecules by affecting protein-protein interactions, affecting the active and inactive state of signalling molecules in terms of transition, or altering the subcellular localisation. Moreover, they have a prominant role in histone-mediated chromatin remodelling and they are considered important for many cellular homeostasis aspects (Ransom et al.2010).
The role of mitochondrial defects and oxidative stress in Alzheimer’s disease
Published in Journal of Drug Targeting, 2019
Badar ul Islam, Nasimudeen R Jabir, Shams Tabrez
Recently, a new screening method, known as redox proteomics has emerged for AD detection. As we know that excess production and deposition of Aβ (1–42) causes the induction of oxidative stress and plays a major role in the pathogenesis of AD. This method is quite helpful in providing insights of susceptible molecular targets towards Aβ (1–42) mediated oxidative stress. Butterfield and Boyd-Kimball [2018] [152] listed carbonylation of several proteins viz. glyceraldehyde-3-phosphate dehydrogenase (GAPDH), malate dehydrogenase (MDH), pyruvate dehydrogenase (PDH), dihydropyrimidinase-related protein 2 (DRP-2), β-actin, α/β-tubulin, proteasome α/β-subunit, glutathione S-transferase etc that has been suggested to be vulnerable towards Aβ(1–42) in various AD models. The common relationship between these diseases suggested that Aβ(1–42) mediated oxidative injury affects the proteins leading to reduced energy metabolism, disturbed neuro-excitation and synapsis, improper protein transport (due to the impaired molecular chaperones and breakage), misfolding of protein resulting its aggregation, abnormal APP processing ultimately contributing to cell death [102]. Redox proteomics method also suggested Aβ (1–42) mediated oxidative injury as the early step of AD progression.
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