COVID-19 activates neuroinflammatory response similar to Parkinson’s

Neurodegenerative disorders

By Michael Woodhead

2 Nov 2022

Australian research has shown that COVID-19 activates the same neuroinflammatory response as Parkinson’s disease.

The discovery identifies a potential future risk for neurodegenerative conditions in people who’ve had COVID-19, but also a possible treatment, according to a Queensland University team led by Professor Trent Woodruff.

The team studied the effect of the virus on human microglia by infecting lab-grown cells, finding that SARS-CoV-2 isolates could bind and enter human microglia in the absence of viral replication.

SARS-CoV-2 was also shown to promote microglial NLRP3 inflammasome activation, a major driver of neurodegeneration.

Co-investigator Dr Eduardo Albornoz Balmaceda said triggering the inflammasome pathway sparked a long term neurodegenerative process in the brain.

“It’s kind of a silent killer, because you don’t see any outward symptoms for many years,” he said.

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

The researchers also found the purified SARS-CoV-2 spike glycoprotein was able to activate the inflammasome pathway in microglia and this was further exacerbated when there were already in LPS-primed proteins in the brain linked to Parkinson’s.

“Spike protein also could prime the inflammasome in microglia through NF-κB signalling, allowing for activation through either ATP, nigericin or α-synuclein,” their paper (link here) in Nature Molecular Psychiatry noted.

“So if someone is already pre-disposed to Parkinson’s, having COVID-19 could be like pouring more fuel on that ‘fire’ in the brain,” said Professor Woodruff.

“The same would apply for a predisposition for Alzheimer’s and other dementias that have been linked to inflammasomes.”

The UQ research also showed that the inflammasome activation was prevented by NLRP3-inhibition, pointing to a potential treatment.

This was supported by findings from a further experiment in which they gave covid-infected micce a class of UQ-developed inhibitory drug that is currently in clinical trials with Parkinson’s patients.

The SARS-CoV-2 infected hACE2 mice treated post-infection with the NLRP3 inhibitory drug MCC950, showed significantly reduced microglial inflammasome activation, and increased survival in comparison with untreated SARS-CoV-2 infected mice.

“We found it [MCC950] successfully blocked the inflammatory pathway activated by COVID-19, essentially putting out the fire,” Dr Albornoz Balmaceda said.

“The drug reduced inflammation in both COVID-19-infected mice and the microglia cells from humans, suggesting a possible treatment approach to prevent neurodegeneration in the future.”

Professor Woodruff said while the similarity between how COVID-19 and dementia diseases affect the brain was concerning, it also meant a possible treatment was already in existence.

“These results support a possible mechanism of microglial innate immune activation by SARS-CoV-2, which could explain the increased vulnerability to developing neurological symptoms akin to Parkinson’s disease in COVID-19 infected individuals, and a potential therapeutic avenue for intervention,” the study authors concluded.

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