Tag: tau protein

Innovation Radar: Probiodrug’s Nature Paper Receives Broad Coverage

This week’s Nature publication by researchers of Probiodrug AG and the University of Virginia has received broad coverage in the international media. In Germany and Austria, it made major news in TV (ARD, MDR, ORF) and radio stations (dlf, MDR, dradio), while in the US Rudy Tanzi, neurogeneticist of Harvard Medical School and an advisor on the Alzheimer problem to US-President Barack Obama, was quoted in ScienceNews as saying: “This opens up a whole new view of the disease.”

Alzheimer researcher Thomas Bayer, Professor of Molecular Psychiatry  at the University of Goettingen added in MDR INFO that the publication was “a very important contribution”, demonstrating that very small amounts of pGlu Abeta were able to drag normal Abeta peptides along into the deadly cascade and that tau protein was essential for the toxic function.

As an example, further reports appeared in Der Standard (Austria) and La Stampa (Italy).

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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