October 16, 2009
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A mixed bag of research reports but nonetheless important and significant…
How MS Drug Works: Glatiramir Acetate (COPAXONE®, Teva Pharmaceuticals) is used for the treatment of patients with Multiple Sclerosis, however, it is not clear how this drug works. In this new study, researchers demonstrate that glatiramir acetate can regulate the formation of myelin, the protective sheath around nerve fibers that is compromised in MS patients. Glatiramir acetate induces the formation of helper immune cells that produce nerve promoting molecules, which in turn stimulate the myelin repair process. The study was led by Dr. V. Wee Yong at the University of Calgary and appears in this week’s issue of The Proceedings of the National Academy of Sciences.
New Target to Fight Diabetes: In genetic knockouts of the Lkb1 gene specifically in beta cells, the insulin producing units in the pancreas, the knockout mice exhibited an increased number of beta cells that were also larger than normal with greater amounts of insulin. When they challenged the knockout mice with a high-fat diet to try to induce diabetes, the mice responded and kept blood glucose levels down. Lkb1 is a tumor suppressor gene that was also known to be involved in energy metabolism but it was unclear whether the Lkb1 protein was associated with diabetes. Dr. Robert Screaton’s group at the Children’s Hospital of Eastern Ontario Research Institute answered this question in a report appearing in this week’s Cell Metabolism. Also noteworthy is that a research team from Israel published a similar study leading to the same conclusions. With these surprising and dramatic results, Lkb1 may represent another therapeutic avenue to treat or prevent diabetes.
Sialyltransferase Crystal Structure Solved: Many important proteins, lipids or sugars are modified by the addition of sialic acid and these steps are essential for a number of processes including cell recognition, cell adhesion and immunogenicity. The key enzyme responsible for catalyzing this reaction is a set of related sialyltransferases (ST). In a Nature Structural and Molecular Biology report published this week, Dr. Natalie Strynadka (University of British Columbia) describes solving the crystal structure of ST and provides the first detailed understanding of the enzyme. Without getting into any molecular jargon, suffice it to say that the structural data brings insight into how the enzyme works and how it achieves specificity, which is useful knowledge for developing prospective inhibitors.
Power of Pheromones: Researchers removed the pheromone-producing cells in fruit flies (male or female) and found that these flies were extremely attractive to normal male fruit flies and also flies of other related species. This contradicts the notion that these chemical signals simply attract one individual to another. Instead, they are part of a complex signaling system used by the flies to recognize and distinguish sexes and species. Other unusual behaviour by male fruit flies without pheromones included trying to copulate with each other’s heads. Dr. Joel Levine and his team at the University of Toronto (Mississauga) describe their research in detail in this week’s edition of Nature.
Beta-globin Switch: A proteomics screen was used to identify the enzyme G9a as the interacting partner of NF-E2, which act together to control expression of the beta-globin genes in red blood cell development. This study provides a clearer understanding of the molecular determinants controlling embryonic expression of beta-globin where G9a acts as a repressor and its transition to adult beta-globin expression where G9a promotes expression. The research team at the Ottawa Hospital Research Institute was lead by Dr. Marjorie Brand and the study appears in the early online edition of the Proceedings of the National Academy of Sciences.
September 11, 2009
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Two great medical discoveries…
Stayin’ Alive: During a stroke, for example, neurons deprived of oxygen undergo cell death. In a recent discovery lead by Dr. Michael Tymianski’s team at the Krembil Neuroscience Centre at Toronto Western Hospital, the protein TRPM7 was found to play a critical role in mediating this detrimental effect. After suppressing TRPM7 expression in a localized region of a rat’s brain, they simulated a stroke by cutting off blood flow to the brain for 15 minutes. The subsequent analysis revealed a complete lack of tissue damage compared to rat brains expressing TRPM7. The resistance to death by cells lacking TRPM7 even preserved the brain’s cognitive function and memory performance following the ‘stroke’. This may have tremendous implications for preventing further cell damage following ischemia in any tissue and is not necessarily limited to the brain, although it is yet to be tested elsewhere in the body
Details of the discovery are reported in the latest edition of Nature Neuroscience.
Insulin Resistance Gene Discovery: An international effort led by Dr. Robert Sladek and Dr. Constantin Polychronakos at McGill University performed a genome-wide comparison and identified a single nucleotide variation in the genetic region near the IRS1 gene that is associated with insulin resistance and hyperinsulinemia.
Dr. Sladek explains it best:
“It’s a single-nucleotide polymorphism (SNP, pronounced ‘snip’), a single letter change in your DNA,” said Sladek. “What’s interesting about this particular SNP is that it’s not linked genetically to the IRS1 gene in any way; it’s about half-a-million base-pairs away, in the middle of a genetic desert with no known genes nearby. In genetic terms, it’s halfway from Montreal to Halifax. And yet we can see that it causes a 40-per-cent reduction in the IRS1 gene, and even more important, a 40-per-cent reduction in its activity. Which means that even if insulin is present, it won’t work.”
IRS1 is known to be the key signalling protein involved in the cell’s initial response to insulin. This recently discovered variant allele affects the level of IRS1 protein expressed and reduces the capacity of the cells to respond to insulin. Unlike other diabetes risk genes that affect insulin production in the body, this is the first that is known to suppress insulin stimulation in the cells.
The research article appears in the early online edition of Nature Genetics.