Scientists at the University of Cambridge have discovered how the body’s ability to get rid of toxic proteins is affected in Huntington’s disease and other forms of dementia.
They have also found that an HIV drug can help to restore this ability, slowing down the disease and reducing the build-up of toxic proteins.
Neurodegenerative diseases, such as Huntington’s disease and various forms of dementia, are caused by the build-up of clusters of misfolded proteins in the brain.
This process leads to the death of brain cells and the onset of symptoms.
One way the body naturally removes toxic materials is through a process called autophagy, where cells break down and discard unwanted material.
However, in neurodegenerative diseases, autophagy does not work correctly, which means that the body is unable to get rid of the misfolded proteins.
In a study published in the journal Neuron, scientists have identified a process that stops autophagy from working properly in the brains of mouse models of Huntington’s disease and a form of dementia caused by the build-up of the tau protein.
The brain and central nervous system have their own specialist immune cells, called microglia, which are supposed to protect against unwanted and toxic materials.
In neurodegenerative diseases, the microglia activate in a way that impairs the process of autophagy.
The scientists discovered that microglia release a group of molecules in response to neurodegenerative diseases.
These molecules activate a switch on the surface of cells called CCR5, which then impairs autophagy, meaning that the brain cannot remove the toxic proteins.
As a result, the proteins aggregate, causing irreversible damage to the brain, and creating a feedback loop that leads to the further build-up of the aggregates.
When the scientists removed the action of CCR5 in mice, they found that they were protected against the build-up of misfolded proteins, leading to fewer toxic aggregates in the brain.
The CCR5 switch is not just used by neurodegenerative diseases—it is also used by HIV as a ‘doorway’ into our cells.
In 2007, the US and European Union approved a drug known as maraviroc, which inhibits CCR5, as a treatment for HIV.
The researchers tested maraviroc in mice with Huntington’s disease and dementia.
When they looked at the mice’s brains, they found a significant reduction in the number of protein aggregates when compared to untreated mice.
The same effect was observed in the dementia mice. Not only did the drug reduce the amount of protein aggregates, but it also slowed down the loss of brain cells.
The treated mice performed better than untreated mice in an object recognition test, suggesting that the drug slowed down memory loss.
Maraviroc may not itself turn out to be the magic bullet, but it shows a possible way forward.
How to prevent dementia
To prevent dementia, it’s important to adopt healthy lifestyle habits, such as regular exercise, a healthy diet, not smoking, limiting alcohol consumption, and getting enough sleep.
Engaging in mentally stimulating activities, such as reading, learning new skills, and socializing, may also help.
It’s also important to manage other health conditions, such as high blood pressure, diabetes, and depression, as these can increase the risk of dementia.
If you care about dementia, please read studies that your walking speed may tell your risk of dementia, and these high blood pressure drugs could prevent dementia.
For more information about brain health, please see recent studies that high-fiber diet could help lower the dementia risk, and these antioxidants could help reduce dementia risk.
The study was conducted by Beatrice Paola Festa et al and published in Neuron.
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