Like a ‘fire in the brain’: COVID can cause brain inflammation that mimics Parkinson’s symptoms

We generally think of SARS-CoV-2, the pathogen that causes COVID, as a respiratory virus. That makes sense, considering it’s airborne and typically infects humans through the nose and lungs, and causes respiratory symptoms like cough and sore throat. But maybe we should start thinking of SARS-CoV-2 as a brain virus as well.

After all, we have hard evidence that SARS-2 can infect the brain, causing lasting, even permanent damage. This can lead to life-threatening strokes and encephalitis, inflammation of the brain or what is colloquially known as “brain fog”.

Even anosmia, the loss of taste and smell – considered a hallmark symptom of this disease, although this is changing – is a neurological disorder, a category of conditions affecting the brain and central nervous system. This includes stroke, epilepsy, Alzheimer’s disease, Parkinson’s disease and meningitis. Remarkably, SARS-CoV-2 appears capable of playing a role in all of these neurological dysfunctions and more.

SARS-CoV-2 even appears to activate the same mechanisms in the brain that can cause Parkinson’s disease, a brain disorder characterized by involuntary movements, tremors and difficulty with balance.

Fortunately, developing these neurological conditions from COVID appears to be rare. The propensity to show such symptoms also depends on the severity of the infection, with vaccinated people usually showing milder or temporary symptoms. Medical history can also play a role in the likelihood of developing neurological disorders. However, age does not appear to be a major factor, as children can also be affected.

We also don’t know what role repeated infections might play in this pathology or whether some viral variants are more prone to neurological damage than others. With a “variant soup” seemingly poised to ravage North America and Europe this winter, experts are still asking a lot of questions about COVID and the brain, but what we’re learning is not reassuring.

What we do know is that SARS-CoV-2 appears to activate the same mechanisms in the brain that can cause Parkinson’s disease, a brain disorder characterized by involuntary movements, tremors and difficulty with balance. A new study published in the journal Molecular Psychiatry shows for the first time that SARS-2 can trigger the same inflammatory processes seen in patients with Alzheimer’s or Parkinson’s disease.

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The good news is that these researchers are identifying a way to stop this process using a drug, which means that in the future there may be a pill to take to prevent brain damage from COVID. . To find out how, an international team of researchers led by Professor Trent Woodruff from the University of Queensland carried out several different experiments, including with mice, African green monkey kidney cells and human immune cells called microglia, which act like white blood cells but specifically protect neurons.

In each of these experiments, the scientists were looking for NLRP3, a type of protein called an inflammasome, which defends the brain against attackers by releasing a mess of inflammatory markers. NLRP3 has been widely studied, with some research implicating this protein for the underlying causes of Parkinson’s disease.

Dr. Albornoz Balmaceda described this cascade of inflammation as a “fire” in the brain, which spreads, killing neurons in its wake.

In each of these assays, whether Petri dishes or animal models, NLRP3 was found to be activated. This means that SARS-2 infection in the brain also appears to activate NLRP3, which could put people at increased risk of developing Parkinson’s disease or related neurological conditions.

“We studied the effect of the virus on the brain’s immune cells, ‘microglia’ which are the key cells involved in the progression of brain diseases like Parkinson’s disease and Alzheimer’s disease,” said Prof. Woodruff in a statement. When his team cultured human microglia in the lab and infected those cells with SARS-2, they showed signs of intense inflammation that are familiar to neuroscientists studying Parkinson’s disease. “We found that the cells did indeed become ‘angry,’ activating the same pathway that Parkinson’s and Alzheimer’s proteins can activate in the disease, the inflammasomes,” Woodruff said.

Dr. Albornoz Balmaceda, another of the study’s authors, described this cascade of inflammation as a “fire” in the brain, which sweeps through, killing neurons in its wake. “It’s kind of a silent killer, because you don’t see any outward symptoms for many years,” Balmaceda said in the same statement.

A fire of anger in the brain sounds bad, but this inflammation actually serves a purpose; this is not an evolutionary error. When a pathogen like a virus crosses the blood-brain barrier, a shield around the brain to filter out unwanted substances, it can start causing damage, infecting neurons and forcing them to shrivel up.

This can trigger the release of NLRP3, which then spreads more inflammatory proteins called caspases. These start telling the damaged cells to die in order to stop the spread of the invader, eliminate the damaged cells and start repairing themselves. This process is called pyroptosis, from the Latin “pyro” for fire and the Greek “ptosis” for falling, like the leaves of a tree. This type of inflammation causes a chain reaction that can kill many neurons like a chain of firecrackers going off.

A small part of this inflammation is natural and can be protective, like a controlled burn. But too much pyroptosis and you go from a contained bonfire to igniting all the wood. As more and more neurons die, the brain begins to malfunction.

To further confirm this theory, the researchers repeated the experiments using a drug that blocked this pathway. Obliquely called MCC950, this drug shuts down NLRP3 signaling and has been used in similar studies related to this inflammation pathway. MCC950 binds to NLRP3, preventing inflammation and preventing the brain from igniting with anger.

MCC950 is currently in development as a way to treat Parkinson’s disease, although some research in mice suggests that MCC950 may have side effects, such as kidney damage. But other similar drugs that stop NLRP3 in its tracks could be pending, so hypothetically a drug like this could also stop some of the ill effects of SARS-CoV-2. We now know at least one of the ways SARS-CoV-2 can wreak havoc on the brain, but we’re also one step closer to finding a cure for this and other neurological conditions. like Parkinson’s disease.

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