Summary: A new study reports that COVID-19 infection activates the same inflammatory response in the brain as Parkinson’s disease.

source: University of Queensland

Research from the University of Queensland has found that COVID-19 activates the same inflammatory response in the brain as Parkinson’s disease.

The discovery identified potential future risks of neurodegenerative conditions in people who have contracted COVID-19, but also a potential treatment.

The UQ team was led by Professor Trent Woodruff and Dr Eduardo Albornoz Balmaceda from the University of Queensland’s School of Biomedical Sciences, and virologists from the School of Chemistry and Molecular Biosciences.

Professor Woodruff said: “We studied the effect of the virus on the brain’s immune cells, ‘microglia’ which are key cells involved in the development of brain diseases such as Parkinson’s and Alzheimer’s.

“Our team grew human microglia in the lab and infected the cells with SARS-CoV-2, the virus that causes COVID-19.

“We found that the cells effectively became angry, activating the same pathway that Parkinson’s and Alzheimer’s proteins can activate in disease, the inflammatory particles.”

Dr. Albornoz-Palmeda said the release of the inflammasome pathway led to a “fire” in the brain, starting a chronic and ongoing process of killing neurons.

“It’s kind of a silent killer, because you don’t see any external symptoms for many years,” said Dr. Albornoz Balmaceda.

“It may explain why some people who have had COVID-19 are more likely to have neurological symptoms similar to Parkinson’s disease.”

The researchers found that the spike protein of the virus was enough to start the process and exacerbate when there were already proteins in the brain associated with Parkinson’s disease.

Professor Woodruff said: ‘If someone really does have Parkinson’s disease, having COVID-19 could be pouring more fuel on that ‘fire’ in the brain.

“The same is true of predisposition to Alzheimer’s disease and other types of dementia that have been linked to inflammatory diseases.”

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The discovery identified potential future risks of neurodegenerative conditions in people who have contracted COVID-19, but also a potential treatment. The image is in the public domain

But the study also found a potential cure.

The researchers administered a class of inhibitory drugs developed by the University of Queensland that is currently undergoing clinical trials with Parkinson’s patients.

“We found that it successfully blocked the inflammatory pathway activated by COVID-19, essentially putting out the fire,” said Dr. Albornoz Balmaceda.

“The drug reduced inflammation in both mice infected with COVID-19 and human microglia cells, suggesting a potential therapeutic approach to prevent neurodegeneration in the future.”

Professor Woodruff said that while the similarity between how COVID-19 and dementia affect the brain was worrisome, it also meant there was already a potential treatment.

“More research is needed, but this is potentially a new approach to treating a virus that could otherwise have unspeakable long-term health repercussions.”

The research was co-led by Dr Alberto Amarilla Ortiz, Associate Professor Daniel Watterson, and involved 33 co-authors from the University of Queensland and internationally.

About this COVID-19 and Neuroinflammation Research News

author: press office
source: University of Queensland
Contact: Press Office – University of Queensland
picture: The image is in the public domain

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original search: open access.
“SARS-CoV-2 drives inflammatory NLRP3 activation in human microglia through spike protein” by Eduardo A. Albornoz et al. Molecular Psychiatry


SARS-CoV-2 induces inflammatory NLRP3 activation in human microglia through the spike protein

Coronavirus disease 2019 (COVID-19) is primarily a respiratory disease, however, an increasing number of reports indicate that SARS-CoV-2 infection can also cause severe neurological manifestations, including cases of probable Parkinson’s disease.

As inflammatory NLRP3 microglia activation is a major driver of neurodegeneration, we inquired here whether SARS-CoV-2 could enhance the activation of inflammatory NLRP3 microglia.

Using SARS-CoV-2 infection of transgenic mice expressing human angiotensin-converting enzyme 2 (hACE2) as a preclinical model of COVID-19, we demonstrated the presence of virus in the brain along with activation of microglia and upregulation of inflammatory NLRP3 compared with non-viral mice. infected.

Next, using a monocyte-derived microglia model, we determined that SARS-CoV-2 isolates can bind to and enter human microglia in the absence of viral replication.

This interaction between virus and glia caused a strong activation of inflammation, even in the absence of another introductory signal. Mechanistically, we showed that SARS-CoV-2 purified glycoprotein activates the inflammatory antibody NLRP3 in LPS microglia, in an ACE-2-dependent manner.

The spike protein can also direct the inflammasome in microglia through NF-κB signaling, allowing activation through ATP, nigericin, or α-synuclein. Of note, glial glial activation mediated by SARS-CoV-2 protein was significantly enhanced in the presence of alpha-synuclein fibrils and completely abrogated by NLRP3 inhibition.

Finally, we showed that hACE2-infected SARS-CoV-2 mice that were orally treated after infection with the NLRP3 inhibitor MCC950 significantly reduced microglia activation, and increased the survival rate compared to SARS-infected mice. -CoV-2 untreated.

These findings support a possible mechanism of glial innate immune activation by SARS-CoV-2, which could explain the increased susceptibility to developing Parkinson’s-like neurological symptoms in individuals with COVID-19, and a potential therapeutic avenue for intervention.

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