Nature cover: Mammalian brain research makes a major discovery

Researchers at the University of Copenhagen have made a breakthrough in further understanding the mammalian brain, and they have made an incredible discovery
.
That is, an important enzyme that activates brain signals is turning on and off randomly, even requiring hours of "rest.
"
These findings could have a major impact
on our understanding of the brain and the development of drugs.
Today, the discovery was on the cover
of Nature magazine.

Millions of neurons are constantly passing information to each other, forming thoughts and memories that allow us to move our bodies
as we please.
When two neurons meet to exchange information, neurotransmitters are transferred from one neuron to another with the help of a unique enzyme
.
This process is essential
for neuronal communication and the survival of all complex organisms.
Until now, researchers around the world thought that these enzymes were active at all times, constantly transmitting the necessary signals
.
But this is far from the
case.
Researchers from the Department of Chemistry at the University of Copenhagen took a closer look at the enzyme in an innovative way and found that its activity switched on and off at random intervals, contradicting
our previous understanding.

"This is the first time anyone has studied these mammalian brain enzymes, one molecule at a time, and we were in awe
of the results.
" Contrary to popular belief, and unlike many other proteins, these enzymes can stop working for a few minutes to a few hours
.
Still, the brains of humans and other mammals are able to perform miraculously," says Professor Dimitrios Stamou from the Centre for Geometric Engineering Cell Systems at the Department of Chemistry at the University of Copenhagen, who led the study
.

So far, such studies have been conducted
with enzymes that are very stable in bacteria.
Using this new method, the researchers studied mammalian enzymes
isolated from rat brains for the first time.

The conversion of enzymes can have a profound effect on the communication of neurons

Neurons communicate
through neurotransmitters.
To transmit information between two neurons, neurotransmitters are first pumped into small membrane sacs (called synaptic vesicles).

The bladder acts like a container for neurotransmitters and releases them
between two neurons only when they are transmitting information.
The central enzyme of the study, known as V-ATPase, is responsible for providing energy
for the neurotransmitter pumps in these vessels.
Without it, neurotransmitters cannot be pumped into containers, which cannot transmit information
between neurons.

But studies have shown that in each container, there is only one enzyme; When this enzyme shuts down, there is no more energy to drive the neurotransmitter into the container
.
This is a completely unexpected new discovery
.

"It's almost incomprehensible that the extremely critical process of loading neurotransmitters in containers is entrusted to only one molecule
in each container.
Especially when we found that 40% of the time these molecules were turned off," said Professor Dimitrios Stamou
.

These findings raise a number of interesting questions: "Does shutting down the energy source of the containers mean that many of those containers are indeed deficient in neurotransmitters?" Does a large number of empty containers significantly affect communication between neurons? If so, is this a problem that neurons evolved to circumvent, or could it be an entirely new way of encoding important information in the brain? Only time will tell
.
”

A revolutionary method for screening V-ATPase drugs

V-ATPase is an important drug target because it plays a key role
in cancer, cancer metastasis, and several other life-threatening diseases.
Therefore, V-ATPase is a profitable target for anti-cancer drug development
.

Existing V-ATPase drug screening methods are based on signaling an average of billions of enzymes simultaneously
.
As long as an enzyme works in time, or when the enzyme works in large numbers in synergy, it is enough to know the average effect of a drug
.

"However, we now know that neither scenario is necessarily true
for V-ATPase.
Therefore, in order to understand and optimize the desired effect of drugs, methods for measuring the behavior of individual V-ATPases suddenly become crucial," said the first author of the paper, Dr.
Elefterios Kosmidis from the Department of Chemistry at the University of Copenhagen, who led the laboratory experiment
.

The method developed here is the first method
that can measure the effect of a drug on a single V-ATPase enzyme molecular proton pump.
It can detect currents
that are more than 1 million times smaller than the gold-standard patch-clamp method.

• V-ATPase is an enzyme
  that breaks down ATP molecules and pumps protons through cell membranes.
  

• They are present in all cells and are essential
  for controlling pH/acidity inside and outside the cell.
  

• In neuronal cells, a proton gradient established by V-ATPase provides energy for loading neurochemical messengers (neurotransmitters) into synaptic vesicles for subsequent release
  at synaptic junctions.