Neuritosis begins in neurites
Researchers have described how neurons stop interacting in Huntington's disease
Dmitry Mazalevsky, Naked Science
Using animal models and laboratory–grown nerve cells, University of Pittsburgh researchers have presented a new mechanism – "neuritosis" - that can explain the disconnection of neurons in Huntington's disease and other neurodegenerative diseases, opening up new therapies.
A distinctive feature of neurodegenerative diseases, such as Huntington's disease, is the progressive death of nerve cells in the brain. However, this process is not so fast and begins with the fact that the cells begin to disconnect from each other, because their neurites become smaller.
"Neuritosis is a process that has not been described so far, it can play an important role in brain development, as well as in aging and neurodegenerative diseases," explains Robert Friedlander, MD and senior author of the work. The study itself is published in the journal Proceedings of the National Academy of Sciences (Baranov el al., Mitochondria modulate programmed neuritic retraction).
It all started with the fact that Sergey Baranov, an employee of Friedlander's laboratory, noticed an interesting phenomenon in the nerve cells of laboratory mice. Their mitochondria–a kind of cellular powerhouse–at the ends of the neurites did not work as well as they should. Paying attention to the neurons in the spinal cord of mice, he discovered the same phenomenon. According to Baranov, unlike other researchers who must have noticed it too, they managed to visualize this phenomenon and suggest a potential cause.
The researchers found that when the proteins in the mitochondria at the ends of the neurites wore out, new proteins to replace them did not arrive as quickly as they did near the nucleus. This made their functioning less efficient, which activated caspases, a family of cysteine proteases that cleave proteins, and eventually led to the death of neurites.
Friedlander and his team called it neuritosis, a variation of apoptosis, a process of cell death that involves the activation of caspase. According to scientists, the processes of neurons are quite long, and the further you are from the nucleus, whose DNA includes many genes necessary for mitochondria to work, the more difficult it is to repair their damage.
To test whether this is related to neurodegenerative diseases, the team of scientists used genetically modified mice with an embedded mutated version of the human huntingtin protein. As a result, the rodents showed characteristic symptoms of the disease, including accelerated death of neurons. The new data were similar to those obtained under artificial conditions, but were more pronounced: fewer mitochondria were contained at the ends, and those that remained turned out to be non-functional. In addition, scientists observed an increased level of cell death.
"It is likely that neuritosis usually occurs among nerve cells and does not necessarily lead to their death, however, in neurodegenerative diseases, the stress level of the already vulnerable ends of neurites increases, which can increase neuritosis, provoking mass cell death. If we can find a way to preserve healthy mitochondria at the nerve endings, it can help in the treatment of neurodegenerative diseases," Friedlander is sure.
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