Thursday, April 15

Neurons know how to repair the genetic damage of aging and disease


Neurons know how to repair the genetic damage of aging and disease

Neurons know how to repair the genetic damage of aging and disease

Scientists from the Salk Institute for Biological Studies have discovered that neurons repair their DNA following a specific plan: their decisions are not random, but respond to specific and specific needs. They need to work permanently on the repair of genetic damage because they are not able to replicate their DNA. The finding of the American researchers could lead to the development of new therapeutic approaches.

According to a release, neurons focus on certain regions of DNA that play a critical role in their identity and function: in this way, they manage to maintain the health of neural circuits. The decline in this self-regenerative capacity over the years would explain the emergence of diseases such as Alzheimer’s, Parkinson’s and other dementias.

Although previous research has focused on identifying the sections of DNA that suffer genetic damage, this is the first time that researchers have looked where the genome is being repaired the most. The findings could be the starting point to explore DNA repair as a therapeutic approach against neurodegenerative diseases.

Unlike other cells, and considering that they cannot replace themselves, cells neurons They are among the longest-lived cells in the human body. Due to this condition, the task of genetic repair that they carry out is even more important: thanks to it, they can remain active and vigorous for a greater amount of time. Now scientists have found this work to be specialized and focused on specific questions.

The neuron plan

The discovery was made by applying an innovative technique to generate neurons from stem cells. These neurons were “fed” with molecules designed to make up building blocks of DNA. The researchers then tracked down these molecules through DNA sequencing and were able to obtain images showing how neurons used them to repair their genome.

Although the experts had already hoped to discover some planning in the genetic repair process, they were amazed to find how strongly neurons were focused on protecting certain sections of the genome. According to the scientists, they observed incredibly sharp and well-defined repair regions: these would be crucial areas for the maintenance of neuronal activity.

At the same time, they were able to verify that the proteins found in these nerve centers are involved in neurodegenerative diseases, while the priority repair regions are also related to aging. In this way, they were able to confirm the “blueprint” that guides neurons in their efforts to repair their genome.

A change of approach and new therapies

Specifically, the researchers found approximately 65,000 priority repair centers, covering about 2 percent of the neuronal genome. According to the scientists, the finding is due to a change in approach: they stopped concentrating on the damaged sectors of the genome to search in the regions that have repairs.

For Fred “Rusty” Gage, one of the authors of the research and President of the Salk Institute, “these findings have enormous potential to change the way we view many age-related diseases of the nervous system. They open a new way to explore DNA repair as a concrete and possible therapeutic approach, “he said.

In the future, the researchers will seek to optimize their method of “detecting” priority areas of genome repair in neurons, to achieve greater precision around how they design and execute their plan. With this information, it will be possible to create therapeutic instruments that reduce the impact of age and aging on neuronal health.

Reference

Incorporation of a nucleoside analog maps genome repair sites in postmitotic human neurons. Fred Gage, Dylan A. Reid et al. Science (2021).DOI:https://doi.org/10.1126/science.abb9032

Photo: Gerd Altmann and Pixabay.

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