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Tag Archives: neurons

Friday Science Review: April 30, 2010

Maybe these primary research projects will lead to the next great “Dendreon” story…

Mirror-rorriM Movement Disorder: Defects in the proper connections between the left and right sides of the brain can lead to involuntary movements where one side of the body follows or mirrors the movement of the other side.  A study of two families affected by inherited cases of mirror movements led to the identification of mutations in the DCC gene (Deleted in Colorectal Carcinoma).  DCC is a receptor for netrin-1, which is a factor that is important for guiding neural axons across the midline to make the proper left-right connections.  This is a key finding in understanding the complexities of how our brains are wired.  Dr. Guy Rouleau (Université de Montréal) and Dr. Frédéric Charron (Institut de recherches cliniques de Montréal) collaborated on the study and is published in the prestigious Science journal.

Improving RNA Therapeutics: RNA interference based therapeutics is gaining traction in the biotech world (eg. Tekmira, Alnylam, MDRNA).  Enhancing the potency of siRNA is the focus of this research study published in Nucleic Acids Research journal.  The technology uses a combination of DNA and RNA analogs to increase the stability of the siRNA agent against nucleases and helps them to evade immune responses that often limit their effectiveness.  Dr. Masad Damha led his group at McGill University.

Also in Montreal, Drs. François Major and Gerardo Ferbeyre (Université de Montréal) announced the launch of the first ribonucleic acid (RNA) engineering laboratory in Canada.  They are using bioinformatics and biochemistry to come up with designer microRNAs that can control the behaviour of RNAs to control or cure cancers.

New Tumour Suppressor:  A recent study demonstrates the tumour suppressor properties of the Cdh11 gene.  The first hint of this function arose from studies showing a frequent loss Cdh11 in retinoblastoma cancers.  Using a series of animal models to determine the role of Cdh11, Dr. Brenda Gallie’s team (Ontario Cancer Institute) demonstrated the tumour suppressor properties of Cdh11 through a mechanism promoting cell death or apoptosis.  The full text article appears online in PLoS Genetics.

Lung Cancer Drug Target: CXCR4 may be the next therapeutic target for treating lung cancer.  Its overexpression in about 10% of lung cancers is associated with poor patient outcome (2.7 vs. 6.1 months survival), likely due to CXCR4’s support for the rapid growth and metastasis of tumours.  On the brighter side, anti-CXCR4 drugs, which are already in existence for the treatment of HIV/AIDS, may be “fast tracked” for testing in lung cancer patients.  Dr. Gwyn Bebb, from the University of Calgary, presented her data recently at the 2nd European Lung Cancer Conference.

Friday Science Review: February 5, 2010

Several neurological related stories this week and quantum biology?

Glial Cells – They’ll turn against you: An unusual molecule can turn glial cells, which normally surround neurons, into killer cells that attack the neurons they are suppose to protect.  Researchers made the surprising discovery of proNGF’s role while trying to figure out its function in the eye.  They found that it can activate glial cells to turn against retinal neurons and potentially cause vision impairment or loss.  Some of the molecular details were also worked out and they describe the significance of TNFalpha and p75NTR proteins in this cell death process.  These results shed light on potential routes for therapeutic targets to prevent certain cases of vision loss.  The study, published in the early on-line edition of the Proceedings of the National Academy of Sciences, is a collaboration involving Dr. Adriana Di Polo at Université de Montreal and Dr. Philip Barker at the Montreal Neurological Institute.

Unexpected Heart Failure and Treatment: Researchers studying mouse models for neuronal diseases, such as Alzheimer’s, noticed progressive abnormalities in the rodent’s heart function.  The mice had slower heart rates (as expected) but they also had difficulty pumping blood and researchers soon realized that they may have stumbled upon a possible mechanism of human heart failure.  The genetic modification in these mice resulted in decreased levels of the neurotransmitter, acetylcholine.  In contrast to previous reports on heart failure, this is the first study suggesting that slower heart rates may lead to cardiac dysfunction.  Furthermore, the administration of the drug Pyridostigmine, which increases acetylcholine levels and is approved for treating muscle weakness, corrected the cardiac dysfunction.  The research team of Drs. Marco Prado and Vania Prado at the Robarts Research Institute at The University of Western Ontario describe their findings in the latest edition of Molecular and Cellular Biology.

Early Stages of Huntington’s: Insight into the cellular mechanisms in the brain that causes Huntington’s disease is described in this article appearing in the journal Neuron.  Using mouse models expressing the gene mutations causing the disease, scientists discovered increased numbers of NMDA receptors surrounding the synaptic connections between neurons.  The increased NMDA receptor activity also diminishes survival signals leading to brain cell death.  In other words, the neurons become confused and triggers cell death (excitotoxicity).  Although it is not known why the receptors accumulate outside of the neuron, a therapeutic drug is already available (for Alzheimer’s) to treat the early stages of the disease.  Memantine can control the abnormal NMDA receptor signaling specifically outside the synapses and not disrupt the normal activity within the synapse, thereby reducing side effects.  Clinical trials are underway.  Dr. Lynn Raymond at the University of British Columbia led the research team.

Algae + Quantum Biology?: It appears that algae, a very simple organism, figured out quantum mechanics nearly two billion years ago.  During the process of photosynthesis, antenna proteins in the light-harvesting complexes absorb light and transmit the energy between molecules to proteins in the reaction centre.  Researchers at the University of Toronto decided to study this energy transfer and discovered quantum mechanics at play in this photosynthetic process.  This is just a bit beyond the scope of our blog but you can read Drs. Greg Scholes and Paul Brumer’s commentary here or enrich yourself with the detailed study here in the journal Nature.

Friday Science Review: December 11, 2009

WOW!  A busy week in the bioscience world…

Pull Down Your ‘SOCS’ and Grow Some Nerves: A long standing question is how to get mature neurons, which stop growing at around the age of two, to start growing again after sustaining nerve damage.  The answer may lie in a protein called SOCS3 (suppressor of cytokine signaling 3).  SOCS3 controls neuronal growth in adults but when it is absent (in a knockout mouse model), axons can regenerate after nerve injury.  This process may be enhanced by supplying a cocktail of neurotrophic growth factors that the researchers also identified in their study.  This is a very important discovery that will push regenerative medicine to new therapeutic strategies.  Dr. Patrice Smith started the research as a postdoctoral fellow at Harvard University and now runs her own lab at Carleton University.  The study is published in the latest edition of Neuron.  There is also an inspirational story about Dr. Smith in the Globe and Mail.

Protecting your Brain after a Stroke: Following a stroke, neurons are at risk of permanent damage caused by overactivation of NMDARs (N-methyl-D-aspartate glutamate receptors).  A key molecular step leading to this excitotoxic neuronal death was discovered in this recent study.  The trauma causes degradation of Insig-1 (insulin-induced gene-1), which triggers the activation of the transcription factor SREBP-1 (sterol regulatory element binding protein-1).  However, when they blocked the activation of SREBP-1 they were successful in reducing the neuronal damage.  This is a promising target for generating therapeutic drugs aimed at minimizing the detrimental effects of strokes and brain trauma.  The research team was guided by Dr. Yu Tian Wang at the University of British Columbia and the study is reported in the latest Nature Medicine.

Breakthrough in Children’s Brain Cancer Research: A rare pediatric brain tumour called Central Nervous System-Primitive Neuroectodermal Tumours (CNS-PNET) offers a very poor prognosis for young patients.  In this gene expression study, a cluster of microRNAs called C19MC was found to be amplified in the diseased tissue in about 25% of the patients. This cluster acts as an oncogene that enhances cell growth and affects differentiation of neural stem cells.   The new discovery will advance opportunities to study this rare pediatric cancer and possibly use C19MC as a diagnostic marker and/or therapeutic target.  The international study was led by Dr. Annie Huang at SickKids Hospital and is reported in the current issue of Cancer Cell.

Genomics Study on Pathogenic Factors: In a large scale study of bacterial genomes, it was proven broadly across microbial species that many of the bacterial virulence factors are contained within genomic islands or clusters of genes.  The virulence factors are proteins that have more “offensive” functions such as toxins that help the bacteria invade the host.  Another significant outcome of this research is the discovery of potentially new pathogen-associated genes that are present pre-dominantly in pathogenic bacteria but less frequently in the non-pathogenic bacteria.  These factors require a closer look as they may represent novel targets for anti-microbial drug development, a critical area of research to combat the increasing prevalence of drug resistant bacteria.   Dr. Fiona Brinkman’s team at Simon Fraser University conducted the research and is detailed in PLoS One.

Dabigatran vs. Warfarin (round 2): Following up on a study that I mentioned here earlier this year, new research further supports the use of Dabigatran over Warfarin.  Patients with a common clotting disorder called venous thromboembolism (VTE) can benefit from Dabigatran as an equally effective and safe blood thinning treatment but without the complications associated with using Warfarin, which requires frequent visits to the clinic for blood monitoring and dosage adjustments.  The study was conducted by Dr. Sam Schulman at McMaster University and appears in this week’s The New England Journal of Medicine.

Research on Congenital Myopathy in Mice:  University of Toronto scientists have generated a mouse model to study a specific type of skeletal muscle disorder.  The mice express a mutant form of the RyR1 protein (type 1 ryanodine receptor/Ca2+ release channel), which causes a severe form of central core disease (CCD). Symptoms in mice that mimic the human condition include progressive congenital myopathy, respiratory stress, skeletal muscle weakness and impaired mobility.  Their study offers insight and future potential to unravel the mechanism behind the disorder.  Dr. David MacLennan’s research is published in The Proceedings of the National Academy of Sciences.

Here is a list of many more important research reports this week from across the country:

Cofactor-activated phosphorylation is required for inhibition of cortical neuron differentiation by Groucho/TLE1. (Dr. Stefano Stifani, McGill University)

Dlx5 Is a cell autonomous regulator of chondrocyte hypertrophy in mice and functionally substitutes for Dlx6 during endochondral ossification. (Dr. Andrew Bendall, University of Guelph)

Pluripotent transcription factors possess distinct roles in normal versus transformed human stem cells. (Dr. Mickie Bhatia, McMaster University)

Nfil3/E4bp4 is required for the development and maturation of NK cells in vivo. (Dr. Tak Mak, The Campbell Family Institute for Breast Cancer Research and University of Toronto).

A novel enediynyl peptide inhibitor of furin that blocks processing of proPDGF-A, B and proVEGF-C. (Dr. Amik Basak, University of Ottawa)

The specificity of the FOXL2 c.402C>G Somatic mutation: a survey of solid tumors. (Dr. David Huntsman, University of British Columbia)

Nuclear function of Smad7 promotes myogenesis. (Dr. John McDermott, York University)

Asf1-like structure of the conserved Yaf9 YEATS domain and role in H2A.Z deposition and acetylation. (Dr. Michael Kobor, University of British Columbia)

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