Copper Homeostasis and Neurodegenerative Disorders (Alzheimer's, Prion, and Parkinson's Diseases and Amyotrophic Lateral Sclerosis)

Antisense promised major advances in treating a broad range of intractable diseases, but in recent years progress has been stymied by technical problems, most notably inadequate specificity, ineffective delivery into the proper subcellular compartment, and unpredictable activity within cells. Herein is an overview of the design, preparation, and properties of Morpholino oligos, a novel antisense structural type that solves the sequence specificity problem and provides high and predictable activity in cells. Morpholino oligos also exhibit little or no nonantisense activity, afford good water solubility, are immune to nucleases, and are designed to have low production costs.

Morpholino antisense oligomers: design, preparation, and properties.

The requirement of the trace element selenium for life and its beneficial role in human health has been known for several decades. This is attributed to low molecular weight selenium compounds, as well as to its presence within at least 25 proteins, named selenoproteins, in the form of the amino acid selenocysteine (Sec). Incorporation of Sec into selenoproteins employs a unique mechanism that involves decoding of the UGA codon. This process requires multiple features such as the selenocysteine insertion sequence (SECIS) element and several protein factors including a specific elongation factor EFSec and the SECIS binding protein 2, SBP2. The function of most selenoproteins is currently unknown; however, thioredoxin reductases (TrxR), glutathione peroxidases (GPx) and thyroid hormone deiodinases (DIO) are well characterised selenoproteins involved in redox regulation of intracellular signalling, redox homeostasis and thyroid hormone metabolism. Recent evidence points to a role for selenium compounds as well as selenoproteins in the prevention of some forms of cancer. A number of clinical trials are either underway or being planned to examine the effects of selenium on cancer incidence. In this review we describe some of the recent progress in our understanding of the mechanism of selenoprotein synthesis, the role of selenoproteins in human health and disease and the therapeutic potential of some of these proteins.

https://www.liebertpub.com/doi/pdf/10.1089/ars.2007.1528

From selenium to selenoproteins: Synthesis, identity, and their role in human health

Selenium is an essential micronutrient with important functions in human health and relevance to several pathophysiological conditions. The biological effects of selenium are largely mediated by se...

https://www.physiology.org/doi/pdf/10.1152/physrev.00039.2013

Selenoproteins: molecular pathways and physiological roles.

Conceptual simplicity, the possibility of rational design, relatively inexpensive cost, and developments in the sequencing of human genome have led to the use of short fragments of nucleic acid, commonly called oligonucleotides, either as therapeutic agents or as tools to study gene function

https://mct.aacrjournals.org/content/molcanther/1/5/347.full.pdf

Antisense Oligonucleotides: Basic Concepts and Mechanisms

Oligomers possessing the Morpholino phosphorodiamidate backbone were evaluated for resistance to a variety of enzymes and biologic fluids. A 25-mer was incubated with nucleases, proteases, esterase...

Resistance of morpholino phosphorodiamidate oligomers to enzymatic degradation.

Purification and properties of selenoprotein W from rat muscle.

Selenoprotein W of rat muscle binds glutathione and an unknown small molecular weight moiety.

/pdf/sequencing-procyanidin-oligomers-by-fast-atom-bombardment-nqquz0mb5f.pdf

Elisabeth Barofsky

Papers

Resistance of morpholino phosphorodiamidate oligomers to enzymatic degradation.

Purification and properties of selenoprotein W from rat muscle.

Selenoprotein W of rat muscle binds glutathione and an unknown small molecular weight moiety.

Sequencing procyanidin oligomers by fast atom bombardment mass spectrometry

Purification, characterization, and glutathione binding to selenoprotein W from monkey muscle.