Tau proteins are best known as the proteins that are stacked to form neuronal "tangles" in Alzheimer's patients' brains, but they also play a role in many other brain disorders such as Parkinson's and Huntington's disease. In healthy circumstances, tau proteins are connected to the cytoskeleton of nerve cells, where they support the cells' structural stability. In the nerve cells of patients, however, tau is dislodged from the cytoskeleton and ultimately tangles together to form protein accumulations that disrupt the nerve cell's functioning.
But even before these protein accumulations are formed, the dislodged tau impedes the communication between nerve cells. VIB's research team has described a new mechanism for this in the journal Nature Communications.
Professor Patrik Verstreken (VIB-KU Leuven) explains: "We have demonstrated that when mutant tau dislodges from the cytoskeleton, it mainly settles at the synapses of the nerve cells. This was not only the case in fruit flies and rats but also in the brain cells of human patients. Vesicles containing chemicals are released at these synapses, which serve as the means of communication between two different nerve cells. When tau settles at the synapse, it locks onto the vesicles, inhibiting synaptic transmission."
Fundamental research with prospects for therapeutic applications
These new insights are the result of a close collaboration between different laboratories at VIB, the universities of Leuven, Louvain-la-Neuve (both in Belgium), and Edinburgh (UK), and with researchers from Janssen Pharmaceutica. They pave the way for a possible treatment.
"Now that we know how tau inhibits synaptic transmission, we can look for ways to prevent it." Patrik Verstreken already provided proof of principle: "If we stop tau from locking onto the vesicles in the nerve cells of rats and fruit flies, we can prevent the inhibition of synaptic transmission and also the death of nerve cells." Further research should reveal whether this strategy will also be useful for patients.
Questions from patients
A breakthrough in research is not the same as a breakthrough in medicine. The realizations of VIB researchers can form the basis of new therapies, but the development path still takes years. This can raise a lot of questions. That is why we ask you to please refer questions in your report or article to the email address that VIB makes available for this purpose: firstname.lastname@example.org. Everyone can submit questions concerning this and other medically-oriented research directly to VIB via this address.
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Zhou, L., McInnes, J., Weirda, K., Holt, M., Herrmann, A. G., Jackson, R. J., ... & Vilain, S. (2017). Tau association with synaptic vesicles causes presynaptic dysfunction. DOI: 10.1038/ncomms15295