One of the topics that my family, especially the older members, always seem to ask me about is Alzheimer's disease and dementia - no one really wants to grow old and at the same time lose touch with reality and themselves. But we really don't seem to know a lot about how our brain protects itself during ageing to explain why this goes wrong in Alzheimer's disease.
So I was intrigued by a paper in Nature from last week, which identified a protein, called REST, that seems to have a key role in protecting against neurodegeneration during ageing.
The authors identified REST while looking for genes whose expression changes during normal ageing. When they explored its function further, they saw that REST protein and mRNA levels were increased in aged brains (specifically in a part of the brain known as the pre-frontal cortex) compared with young adult brains, and that binding of REST to its binding domain on target genes also increased, suggesting an increase in function. What was key was that REST was absent or almost absent from the brains of those with mild cognitive impairment or Alzheimer's disease.
So, what does REST do in the normal aged brain that is missing from the brains of those with Alzheimer's disease? In simple words: in the difficult conditions of oxidative stress (caused by high levels of reactive oxygen species), REST protects normal neuronal cells and stops them from dying.
The authors found that REST is expressed in response to oxidative stress, which is known to be involved in Alzheimer's disease) and that it protects neuronal cells from oxidative damage. At the same time, REST was found to block the expression of genes that promote cell death and genes that are involved in Alzheimer's disease pathology such as presenilin 2, likely through an epigenetic mechanism. As a result, neuronal cells lacking REST that were subjected to oxidative stress showed increased degeneration and cell death.
And this was not just in cells in culture: mice lacking REST showed progressive neurodegeneration, consistent with a neuroprotective role for REST, and C. elegans worms lacking genes that structurally resemble REST showed reduced survival when exposed to oxidative stress conditions compared with normal worms.
What this would suggest is that those individuals with high levels of REST would be protected from Alzheimer's disease. Indeed, this is what the authors observed: among individuals meeting the pathological criteria for Alzheimer's disease, REST levels were significantly higher in those who had preserved their cognitive function than those who were cognitively impaired.
This doesn't of course mean that a cure for Alzheimer's is imminent, but we are now one step closer to understanding this disease, and it is possible that targeting this protein may offer a therapeutic solution for Alzheimer's and other neurodegenerative conditions.
So I was intrigued by a paper in Nature from last week, which identified a protein, called REST, that seems to have a key role in protecting against neurodegeneration during ageing.
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| Image from https://www.flickr.com/photos/lizhenry/2051224366/sizes/s/ |
The authors identified REST while looking for genes whose expression changes during normal ageing. When they explored its function further, they saw that REST protein and mRNA levels were increased in aged brains (specifically in a part of the brain known as the pre-frontal cortex) compared with young adult brains, and that binding of REST to its binding domain on target genes also increased, suggesting an increase in function. What was key was that REST was absent or almost absent from the brains of those with mild cognitive impairment or Alzheimer's disease.
So, what does REST do in the normal aged brain that is missing from the brains of those with Alzheimer's disease? In simple words: in the difficult conditions of oxidative stress (caused by high levels of reactive oxygen species), REST protects normal neuronal cells and stops them from dying.
The authors found that REST is expressed in response to oxidative stress, which is known to be involved in Alzheimer's disease) and that it protects neuronal cells from oxidative damage. At the same time, REST was found to block the expression of genes that promote cell death and genes that are involved in Alzheimer's disease pathology such as presenilin 2, likely through an epigenetic mechanism. As a result, neuronal cells lacking REST that were subjected to oxidative stress showed increased degeneration and cell death.
And this was not just in cells in culture: mice lacking REST showed progressive neurodegeneration, consistent with a neuroprotective role for REST, and C. elegans worms lacking genes that structurally resemble REST showed reduced survival when exposed to oxidative stress conditions compared with normal worms.
What this would suggest is that those individuals with high levels of REST would be protected from Alzheimer's disease. Indeed, this is what the authors observed: among individuals meeting the pathological criteria for Alzheimer's disease, REST levels were significantly higher in those who had preserved their cognitive function than those who were cognitively impaired.
This doesn't of course mean that a cure for Alzheimer's is imminent, but we are now one step closer to understanding this disease, and it is possible that targeting this protein may offer a therapeutic solution for Alzheimer's and other neurodegenerative conditions.
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