So that was a very kind of good collaboration because we had students coming from Russia and Ukraine to my lab at the Max Planck or here at the Hanover Medical School. And I had the great pleasure to be able

to train wonderful students. We also published four papers, two more papers are on the way. So it was a really, really great collaboration and it's sadly that it ended as it ended. So let me take you to the world now of our research and we study neurodegenerations.

And it's kind of a very sad topic because the world population is aging and this increases the number of dementia and other neurodegenerative diseases. Currently, every three second, one person on earth

is diagnosed with dementia. If the dementia would be the economy, it would be the largest economy in the world because the cost of treating dementia and taking care of demented people takes a lot, a lot of money.

And sadly, the numbers are growing and it's expected that by 2050, more than 130 million people on this earth will have some kind of dementia. And why those diseases are so difficult to cure or let's say incurable?

This is because we are dealing with neurons that the cells that never divide, so do not reproduce and therefore they cannot be replaced. But we can prevent dementia and somehow study them. Also, what is the cause of those neurodegenerative disorders?

There are different, of course, causes. There are mutations, but this is rare. Aging is the largest risk factor, but also pollution and addition of different toxic elements to the food. So interestingly, there is this gene

called neuropathy target esterase. Mutations in which cause genetic disorders, but also neuropathy target esterase interacts with organophosphates that can be found in, for example,

different pesticides and insecticides or in germ-like syndrome. And then this also causes neurodegeneration that has a delayed effect. So we can induce the neurodegeneration by different toxins. And neuropathy target esterase

is a phospholipase that regulates lipid metabolism in the membranes. And even though at the biochemistry level, we very well understand what this protein does, we do not know how this protein is causing neurodegenerations.

Humans are very bad model to study in neurodegenerations. First of all, they live very long. There are no controls, and we cannot tell them what to eat and what to do, so not a good model. At the same time, Drosophila is an excellent model because they live only 30 days.

They have more than 70% of all human associated with diseases, genes, homologous. And of course, they have all the organs that we would like to study, including brains. In Drosophila, there is a human ortholog for NTE,

and it is called Swiss cheese. And it's called Swiss cheese because when you have a mutation in the gene, then in the brain, the huge vacuoles appear that called Swiss cheese, and this is due to neuron degeneration. And flies with this mutation have shortening lifespan, abnormal locomotor behavior,

progressive neurodegeneration, and also the appearance of those vacuoles in the brain. So when we looked where Swiss cheese is expressed, we found that it is expressed on the surface of the brain and this surface is a very interesting structure. This is the blood-brain barrier.

And all of us have this blood-brain barrier. This is to protect brain neurons in the brain from all toxins and everything that is in the blood that can happen, whatever exposures we have in the brain. And so if this brain blood barrier is leaking,

then unwanted substances can go inside the brain. And of course, this can cause neuron degeneration. And so what, in Drosophila, this blood-brain barrier is made by two types of glia that makes really, really tight junctions and does not allow anything to come in.

So when we looked at Swiss cheese mutants, we found that in control, they have very nice here structure of this barrier while in mutants, there are a lot of those kind of hyper-wrapping.

Then we, of course, looked if we can rescue this phenotype with human gene because it would mean that the gene has a concert function. And of course, it was very good for us

to see that overexpression of this human gene can rescue the phenotype, cause the mutation of Drosophila gene. And then of course, we wanted to see if this barrier is broken or functional in the mutants. And the experiment is very interesting because you inject this dye into the stomach of the fly

and then you wait until the next day and look if the dye could penetrate the brain. And in controls, this never happened, as you can see here. While in mutants, the dye comes in

and then you can see it inside the brain. So we also quantify those phenotypes and saw that blood barrier integrity is broken and this phenotype can be also rescued by human mutants, but human gene.

Then we said, okay, why do those neuron dye in the brain of mutant flies? And we suggested that it may be due to induced inflammation. We measured inflammatory peptides and we found that those flies have induced inflammation in the brain and we could rescue this inflammation

by adding sodium salicylide and rapamycin, which are the most commonly used drugs that are anti-inflammatory. And recent data suggests that neuroinflammation is one of the most important causes of brain degeneration upon changing.

And so we suggested that maybe this biochemical pathway that is broken in the Swiss cheese mutants leads to the increase of some pro-inflammatory components and such a component is arachidonic acid that is a precursor for echocyanoids

and prostaglandins, if you know about them. So we really saw that our mutants have increased levels of arachidonic acid in the brain. And what we think is happening is that abnormal lipid metabolism is causing the increase of those fatty acids

that should not be present in the brain. This leads to the induction of pro-inflammatory fatty acids and causes inflammation. And then upon a kind of constant inflammation,

the neurons are degenerating and this causes brain degeneration. Importance of this is that we can rescue this phenotype because at least in flies, we were able to rescue this phenotype

with normal anti-inflammatory drugs and also restricted dietary. So this also allow us to think about maybe approaching human disorders. So there is a chance to cure the disease. And so there is a chance. And so I would like to thank the people who did the work

and Mariana who is present in the audience did all the job.