MIT researchers have shown that an enzyme called HDAC1 helps repair damage to neuronal DNA and help fight cognitive decline in age. A discovery representing real hope for patients with neurodegenerative diseases, such as Alzheimer’s.
A pivotal study
If the lesions of theDNA are common to all of our cells, our bodies can repair them quite effectively up to a certain age. Unfortunately, this ability weakens over time, causing many symptoms of aging that we know only too well. As part of this new study published in the journal Nature Communications, a team of researchers from MIT discovered that reactivation of a certain enzyme improves repair of damage to theNeuronal DNA, thereby helping to combat age-related cognitive decline.
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Whereas previous work had shown that this enzyme, called HDAC1 appeared to be involved in repairing theNeuronal DNA, as part of this new study, the team looked at what happened when theHDAC1 was not doing its job.
To do this, the team compared the evolution of genetically modified mice deficient in HDAC1 to that of healthy mice. If there was no difference in terms of damage to theDNA or behavior between the two groups during the growth phase of the animals, the decline then became evident.
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The researchers found that older mice deficient in HDAC1 exhibited greater amounts of damage to theDNA neuronal as well as synaptic plasticity, characterizing the fact that the brain changes the connections between neurons to learn and remember, reduced, which resulted in poorer performance in memory and spatial navigation tests.
Cognitive functions greatly improved in elderly specimens thanks to the reactivation of HDAC1
Upon closer examination of the rodents, the team found that they had lesions of 8-oxo-guanine, a specific type of damage to theDNA caused by oxidation. Knowing that high levels of this type of lesion have also been observed in patients with the diseaseAlzheimer.
” HDAC1 seems to be an anti-aging molecule “, valued Li-Huei Tsai, lead author of the study. ” I think this is a discovery of basic biology with very broad applications, given that a large part of human neurodegenerative diseases only occur during aging. Activation of HDAC1 may be beneficial in many cases. “
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To go further, the researchers then tried to treat the disease using exifone, a drug compound that activatesHDAC1 and used in the past to treat dementia. This was given to mice withAlzheimer and healthy older mice, and the team found that, overall, it reduced lesions of theDNA in the brain, thereby improving cognitive functions like memory.
However, as promising as exifone may seem, this type of treatment is far from ideal (the one that has indeed caused liver damage in some patients). Nevertheless, researchers say that confirming the role ofHDAC1 in reversing cognitive decline means that other drugs fulfilling the same function could be developed.
” This study really positions HDAC1 as a potential new drug target for age-related phenotypes, as well as for pathologies and phenotypes associated with neurodegeneration “, Concludes Tsai.
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