Having expelled toxic protein complexes from themselves through intercellular nanotubes, neurons begin to feel better.
When a cell accumulates too many defects and molecular debris, it switches on a program of careful self-destruction – what is left of it will be picked up and digested by others, and a new cell formed from the stem cell will take its place. However, not everyone can afford to do this. Take neurons, for example: it is believed that in the adult brain of mammals, new neurons are formed to some extent, but the activity of the stem neural precursor cells is clearly not enough to replace neurons if they suddenly wanted to die at the speed of blood cells or intestinal epithelium. (Not to mention the fact that the formation of new neurons in humans is still a subject of active discussion.)
In general, neurons are required to stay alive as long as possible, getting rid of dangerous garbage as efficiently as possible. Among the molecular garbage, some proteins that can stick together into toxic aggregates pose a particular threat. Such aggregates prevent neurons from working, gradually leading to their death, and it is the accumulation of toxic protein complexes that is associated with neurodegenerative diseases such as Alzheimer’s or Parkinson’s. You can get rid of dangerous proteins by somehow digesting them inside yourself, or simply throwing them out, or purposefully fusing them to other brain cells – microglial ones.
Microglia are often called the brain’s immune system: although their cells are different in origin from the cells of the real immune system, they perform roughly the same functions, that is, they hunt pathogens and remove various debris. If neurons and microglia cells are obtained from nerve stem cells in a laboratory, then, by growing them together, you can see how the thinnest threads stretch between them. These threads were discovered several years ago and called tunneling nanotubes. It can be assumed that some proteins, protein complexes, and even entire organelles travel from cell to cell along tunneling nanotubes. In a recent article in the journal Neuron It is said that everything is so.
This time, the researchers experimented with real, natural neurons and microglia taken from mouse and human brains. Nanotubes between them could be seen right in the tissue samples. Growing in a joint culture, the cells began to form tubes when aggregates of the protein α-synuclein were injected into the neurons. It is one of those proteins that stick together to form toxic complexes; complexes of α-synuclein are characteristic of Parkinson’s disease. Aggregates of the protein tau, which appear in Alzheimer’s disease, were also injected into the neurons. Tau aggregates did not stimulate the formation of tubes, but if there were tubes, they, like α-synuclein aggregates, left the neuron along them. The toxic complexes went only in one direction, from the neuron to the microglial cell. And this was visible not only in the laboratory cell culture, but also in the living brain of a mouse, into which neurons with protein aggregates inside were implanted – such neurons extended tubes to local microglial cells, and then the same proteins appeared in the tubes “for release”.
The fact that neurons fused toxic protein complexes through nanotubes benefited the cells themselves: they died less often and retained healthy excitability. And it was not limited to just dumping garbage. Toxic protein complexes harm the cell’s energy organelles, the mitochondria. Microglial cells sent healthy mitochondria through nanotubes to neurons, and it was largely thanks to the donated mitochondria that the neurons began to feel good.
Toxic protein aggregates travel through tunneling nanotubes from neurons to microglial cells; in turn, microglial cells send healthy mitochondria through the same nanotubes to neurons. (Illustration from Nature).
Something similar happens between neurons and other auxiliary cells of the nervous system, astrocytes: we once wrote that astrocytes also share cellular “batteries” with neurons that have found themselves in a difficult life situation. It is also known that microglia cells form a nanotubular network among themselves as well. However, it is unclear to what extent the discharge of dangerous proteins through nanotubes and the exchange of mitochondria between neurons and other brain cells really helps neurons survive. As was said above, unpleasant molecular garbage can simply be thrown outside, and someone will eat it there. If we talk about shares and percentages, then so far in the experiment it is very difficult to separate this method of cellular purification from the nanotube one.
There are also many questions regarding the nanotubes themselves. How often do they form, what stress factors play a role here, does the type of neuron matter (of which, as we know, there are a great many), and finally, how do cells manage to organize the flows of protein complexes and mitochondria only in one direction, that is, protein complexes from neurons, mitochondria from microglia? Obviously, cytoskeletal proteins and intracellular transport should be at work here, but there are clearly not enough details here. Be that as it may, these tubes themselves are quite an interesting phenomenon, so they will be studied further, especially since they really can be related to the development of neurodegenerative diseases.
Source: www.nkj.ru
