This sounds like following this up might solve a couple of these 5 causes of the neuronal cascade of death. But this won't occur because our fucking failures of stroke associations do not follow up research at all. No translational studies, no protocols, all nothing.
http://www.alphagalileo.org/ViewItem.aspx?ItemId=161641&CultureCode=en
In the brain, patterns of neural activity are perfectly
balanced. The interplay between activating and inhibitory
neurotransmitters ensures that the level of activity stays within the
physiological range. During an epileptic attack excitation gains the
upper hand resulting in the death of neurons. Researchers of the Bonn
University Medical School have now discovered a key player in a signal
transduction cascade, which protects neurons from
hyperexcitation-induced cell death. These results open a new direction
for the development of novel therapy options. The results are now
published in „The Journal of Neuroscience“.
Pathophysiological activity often triggers neuronal cell death. This
can for example be observed after an epileptic insult. The cause for
this hyperexcitation is excessive release of the signaling molecule
glutamate. “This neurotransmitter can switch on signaling cascades that
act neurotoxic”, says Prof. Dr. Schoch McGovern of the Institute of
Neuropathology and the Department of Epileptology at the University
Clinic Bonn. However, neurons try to protect themselves and prevent the
damaging hyperexcitation.
The molecular nature of these “body guards” is so far unresolved.
Accumulating evidence shows transcription factors to play an essential
role in the processes by which neurons protect themselves. These factors
switch on certain genes, which then via signal transduction cascades
result in the production of neuroprotective substances. These in turn
counteract the damaging glutamate-induced hyperexcitability.
Increased neuronal cell death in the absence of Syt10
The team of Prof. Dr. Schoch McGovern could now show that the protein
Synaptotagmin 10 (Syt10) is an integral part of this protective shield.
If rats for example experience an epileptic seizure, the amount of
Syt10 in the hippocampal formation of the brain strongly increases. The
researchers used neurons from mice, in which the Syt10 gene had been
ablated, and stimulated them with a glutamate like substance. This
treatment resulted in substantial neuronal death.
NPAS4 modulates the production of protective factors
The research team discovered, which transcription factor activates
the gene for Syt10 in response to pathophysiological neuronal activity.
This essential member of the neuronal body guard is called NPAS4. The
researchers cultured rodent neurons and added several transcription
factors. NPAS4 activated the Syt10 gene and required Syt10 to exert its
neuroprotective function. “NPAS4 triggers a signaling cascade that
results in the production of neuroprotective factors”, says Prof. Dr.
Schoch McGovern.
Search for novel therapy approaches
The molecular identity of the neuroprotective substances is still
unknown. “A potential candidate, the insulin-like growth factor IGF-1,
was not able to reverse the increased neuronal cell death in the absence
of Syt10”, reports the neurobiologist. The next step therefore is to
test other substances. Once the identity of the neuroprotective body
guards is revealed, novel avenues for therapy development open up, for
example for stroke and epilepsy patients. “The goal would be to
administer these protective substances from the outside in order to
prevent neuronal cell death in the brain”, says Prof. Dr. Albert Becker,
a medical doctor, who was part of the study. However, there is still a
long road ahead.
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