DNA damage in microglia leads to age-related neurodegeneration

What is it about?

Neuroinflammation is a major risk factor for challenging neurodegenerative disorders. IMBB researchers have found that persistent DNA damage leads to the accumulation of cytosolic DNA fragments in microglia, stimulating a viral-like immune response in Er1Cx/− and naturally aged mouse brains. They also show that microglia release cytosolic DNAs in extracellular vesicles, causing neuronal cell death. Building on these findings, IMBB researchers developed an anti-inflammatory approach to target activated brain microglia in vivo, eliminate cytosolic DNAs, and postpone the early onset of neurodegeneration.

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Photo by National Cancer Institute on Unsplash

Photo by National Cancer Institute on Unsplash

Why is it important?

Until recently, endogenous DNA damage in post-mitotic neurons was thought to be the primary cause of age-related neurodegenerative disorders . Besides neurons, brain degenerative changes involve the dysfunction of astrocytes, microglia and oligodendrocytes, leading to neuronal cell death. The current work provides evidence that microglial cells can causally contribute to age-related neurodegenerative disorders, irrespective of other cell-autonomous neuronal deficits.

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