Tag: Nature

Company News: Probiodrug AG, Collaborators Explain Interplay of Key Suspects in Alzheimer’s Disease

Nature paper demonstrates that toxicity in AD is induced by pyroglutamate Abeta and is tau protein dependent

Pyroglutamate Ab (“pyroglu Ab”) a predominant, highly toxic fraction of Aβ found in the brains of Alzheimer’s disease patients, triggers the formation of toxic oligomers exhibiting prion-like behavior and initiating neurotoxicity via a tau protein-dependent pathway, thereby explaining the crucial role of such modified Aβ in the onset and spread of neuronal toxicity in Alzheimer’s Disease.

HALLE/SAALE, Germany, May 2, 2012 – Probiodrug AG (Probiodrug), a biotech company developing products for the treatment of neurodegenerative and inflammatory diseases with a particular focus on Alzheimer’s disease (AD), today announced its scientists and academics collaborators published seminal findings on the role of pyroglu Aβ in AD pathology in the May 2, 2012 online edition of the journal Nature (DOI: 10.1038/nature11060). The new findings add to the growing body of evidence that pyroglu Aβ plays a crucial role in the initiation of AD. In addition, the research results further elucidate the mechanism by which pyroglu Aβ triggers neuronal toxicity.

The data published today suggest that pyroglu Aβ  co-aggregates with “normal” Ab peptides to form low molecular weight oligomers (LMOs), which are structurally distinct and far more toxic to cultured neurons than oligomers derived from normal Aβ. Moreover, the presence of the neuronal protein tau is essential for toxicity mediated by LMOs that contain pyroglu Aβ.  The results have been substantiated in transgenic mice designed to express increased levels of pyroglu Aβ. In these animals, the pyroglu Aβ-mediated neuronal loss and gliosis was prevented, if tau expression was shut down. The study is supplemented by results published in the Journal of Neurochemistry. Here the Probiodrug researchers reveal, that the aggregation propensity is caused by the hydrophobic nature of pyroglu Aβ.

The scientists also were able to demonstrate that the cytotoxicity is propagated by a prion-like templating mechanism of Ab misfolding initiated by pyroglu Ab: even after strong dilution to a solution containing only 0.000625% pyroglu Ab, the mix after 24h developed enough toxicity to kill 50% of neurons treated with it.

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Food for Thought: Weekly Wrap-Up

Volker Stollorz in Frankfurter Allgemein Sonntagszeitung (FAS) this week in detail reports on a paper describing the generation of pluripotent stem cells from adult human testis, which has raised suspicions because as yet no one has been able to reproduce the data or cell lines. The paper published 2008 in Nature raised high hopes about the generation of pluripotent human stem cells for research and therapy without technically or ethically debatable interventions. The research originated in the lab of Thomas Skutella, then at the University of Tuebingen, Germany; lead author was Sabine Conrad. Already, researcher Hans R. Schoeler in the same journal expressed concerns that the cells used by Conrad et al. are not pluripotent as described. The article by Stollorz is not yet available online.

Stephan Sahm in Frankfurter Allgemeine Zeitung (FAZ) introduces the new medical discipline of neurogastroenterology which deals with the nerve cells lining the human digestive tract. Already it is known that impairments of these nerve cells lead to motility disturbances of the colon – often seen in diabetics – and to dysfunctions of the immune system.

In the same paper, Hildegard Kaulen describes attempts to understand and cure chronic fatigue in cancer patients. The syndrome often appears after successful tumor eradication by chemo- or radiation therapy and has been neglected by clinicians and doctors in the past.

In Die Welt, Joerg Zittlau introduces a new silicon-based coating developed by Nanopool GmbH. The liquid glass coating is non-toxic, heat- and scratch-resistant and extremely thin and flexible. It is made by extracting nano-sized silica crystals from sand which are subsequently mixed with water and alcohol and applied either manually or by spraying. Once the solvent has evaporated, the glass coating is ready. As it is extremely smooth it is not only suited as protectant but also stain-resistant and self cleaning.

Wolfgang S. Merkel, also in Die Welt, explains why certain materials such as asbestos or nanotubes are dangerous for cells. If particles have a rounded tip they are mistaken by the cells for a small spheric particle and taken up. As the process cannot be terminated for the length of the particle, the cell eventually dies and, if many cells are affected, inflammation and cancer may arise.

Christina Berndt in Sueddeutsche Zeitung (SZ) deals with the latest conspiracy theory spread by ecological fundamentalists: milk is dangerous for toddlers as it blocks the mucosa with phlegm so that it cannot ward off infections. In the same paper, Berndt reports on fundamentalist Taliban in Pakistan opposing vaccination. As a result, polio cases have risen dramatically in the areas controlled by the Taliban.

Hartmut Wewetzer in Der Tagesspiegel introduces latest findings demonstrating that neither resveratrol, the highly acclaimed ingredient of grapes, nor sirtuin proteins guarantee longer, healthier life. Previously, researchers from the US had claimed that sirtuin proteins, which are activated by resveratrol, mediate longer life. In contrast, Nicholas Wade in The New York Times reports on the same study and points out that there is a trans-atlantic rift in reporting: while British scientists say sirtuins are not involved in longevity, the US colleagues under attack say they adhere to their claim. The controversy is around the genetic uniformity or diversity of the animal strains used in the experiments.

Larry Husten in Forbes is commenting on the decline of cardiovascular procedures observed in US hospitals, speculating that four factors may contribute to it: concerns about stent overuse, the payoff of preventive drug treatments, the larger economic climate and recent investigations into implantable cardioverter defibrillator (ICD) by the US Department of Justice. Recently, doctors and hospitals in the US were accused to implant ICDs without proper evidence base in more than 1 in 5 cases.

Also in ForbesDavid Shaywitz and Dennis Ausiello in a commentary demand that doctors translate research results into clinical progress much better than today. The authors do not focus on the “translational science” buzzword but propose simple things: improvements in measurements, a less intrusive medicine and better participation of patients, e.g. by involving Facebook- or smartphone-based information transfer for better compliance and health status surveillance.

In the New Scientist, Debora MacKenzie reports on Sanofi-Pasteur signing a contract with the University of San Diego, Calif. to develop a vaccine for the prevention and treatment of acne, a disease affecting 85% of teens. The challenge: killing the disease-causing bacterium (which is benign under normal circumstances and turns nasty only in clogged sebaceous glands in the skin) is likely to disturb the important, delicate balance of the skin’s normal bacterial community. The solution may be to use an antibody directed specifically against a protein released by the acne-causing bacteria, if  oxygen levels fall below normal in the clogged glands. This approach may neutralize the acne factors and prevent inflammation while leaving the normal bacterial community on the skin undisturbed.

Last not least, physics nerds make a laughing matter of CERN’s latest discovery that neutrinos may travel faster than light, reports Holger Dambeck in Der Spiegel. Our favorite one (true Monty Python style) is as follows: “To reach the other side. Why do neutrinos cross the road?”