Harvard Scientists Uncover New Strategy for Repairing DNA Damage in Neurons

Neuron Illustration

Researchers at Harvard Medical School have identified a DNA repair mechanism in neurons, involving a protein complex called NPAS4-NuA4. This discovery may help explain neuronal longevity and could lead to a better understanding of neurodegenerative diseases.

Researchers discover a mechanism used by neurons to repair damage that occurs during neuronal activity.

  • Researchers have uncovered a novel mechanism for repairing DNA damage in neurons
  • The study reveals a protein complex that initiates a pathway to repair DNA breaks induced by neuronal activity
  • “More research is needed, but we think this is a really promising mechanism to explain how neurons maintain their longevity over time,” said researcher Elizabeth Pollina​​​​​​​

“Use it or lose it” goes the adage, applied liberally to everything from our muscles to our minds, especially as we age.

Yet when it comes to the brain, such usage is not entirely a good thing: While using brain cells may indeed help maintain memory and other cognitive functions throughout life, scientists have found that the associated activity also damages neurons by inviting more breaks into their DNA.

Which raises the question: How do neurons remain healthy and functional over a lifetime of carrying out their vital work in the brain?

Now, a team at Harvard Medical School has identified a novel mechanism of DNA repair that occurs exclusively in neurons, some of the longest-lived cells in the body. The research, conducted in mice and published recently in the journal Nature, helps explain why neurons continue to function over time despite their intense repetitive work.

Specifically, the findings show that a protein complex called NPAS4NuA4 initiates a pathway to repair DNA breaks induced by activity in neurons.

“More research is needed, but we think this is a really promising mechanism to explain how neurons maintain their longevity over time,” said co-first author Elizabeth Pollina, who carried out the work as a research fellow at HMS, and is now an assistant professor of developmental biology at the Washington University School of Medicine.

If the findings are confirmed in further animal studies and then in humans, they could help scientists understand the precise process by which neurons in the brain break down during aging or in neurodegenerative diseases.

A biological contradiction

Within the vast landscape of cell types in the body, neurons stand apart: Unlike most other cells, they do not regenerate, or replicate. Day after day, year after year, they work tirelessly to remodel themselves in response to environmental cues, ensuring that the brain can adapt and operate over a lifetime.

1 Comment on "Harvard Scientists Uncover New Strategy for Repairing DNA Damage in Neurons"

  1. Raji Heyrovska | April 24, 2023 at 1:07 pm | Reply

    Dear Dr. Greenberg,
    I saw your latest research involving DNA damage.
    This paper might interest you:
    “New insight into DNA damage by cisplatin at the atomic scale”
    Author: R. Heyrovska
    a) Nature Precedings http://precedings.nature.com/documents/6891/version/1
    Presented at: the 12th Eurasia Conference on Chemical Sciences, Corfu, Greece, April 16-21, 2012. (Invited talk) Abstract in:
    b) http://eurasia12.uoi.gr/Abstracts_pdf/%281%29%20Bioinorganic/S1%20ORAL/OP8_Abstract_Heyrovska_Eurasia12.pdf
    ……….

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