May 19, 2017
Tau
proteins are involved in more than twenty neurodegenerative diseases, including
various forms of dementia. These proteins clump together in patients' brains to
form neuronal tangles: protein aggregation that eventually coincides with the
death of brain cells. Prof. Patrik Verstreken's research team (VIB-KU Leuven)
has now discovered how tau disrupts the functioning of nerve cells, even before
it starts forming tangles. They immediately suggest a way to intervene in this
process.
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.
Early
spoilsport
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.
More
information: Lujia Zhou et al, Tau association with
synaptic vesicles causes presynaptic dysfunction, Nature Communications
(2017). DOI: 10.1038/NCOMMS15295
Provided by: VIB (the Flanders Institute for Biotechnology)
https://medicalxpress.com/news/2017-05-tau-synaptic-transmission-early-stage.html
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