COVID-19 activates the same inflammatory response in the brain as Parkinson’s disease and other neurodegenerative conditions, according to research led by University of Queensland (UQ), Australia. This group’s findings may explain why some people who have had COVID-19 are more vulnerable to developing neurological symptoms. The team also found a potential treatment for this condition.
The UQ team was led by Trent Woodruff and Eduardo Albornoz Balmaceda from the university’s School of Biomedical Sciences and virologists from the School of Chemistry and Molecular Biosciences. It was published in Nature’s Molecular Psychiatry.
“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 and Alzheimer’s,” Woodruff said.
Microglial NLRP3 inflammasome activation is known to be a major driver of neurodegeneration. The UQ group looked at whether SARS-CoV-2 can promote microglial NLRP3 inflammasome activation.
“Our team grew human microglia in the laboratory and infected the cells with SARS-CoV-2, the virus that causes COVID-19. We found the cells effectively became ‘angry’, activating the same pathway that Parkinson’s and Alzheimer’s proteins can activate in disease—the inflammasomes,” Woodruff said.
Triggering the inflammasome pathway sparked a “fire” in the brain, which begins a chronic and sustained process of killing off neurons, said Balmaceda.“It’s kind of a silent killer, because you don’t see any outward symptoms for many years,” he added.
The researchers found the spike protein of the virus was enough to start the process, which was further exacerbated when there were already proteins in the brain linked to Parkinson’s.
“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,” Woodruff said. “The same would apply for a predisposition for Alzheimer’s and other dementias that have been linked to inflammasomes.”
The study also suggests a potential treatment.
The researchers administered a class of UQ-developed inhibitory drugs, which are currently in clinical trials with Parkinson’s patients. They found that SARS-CoV-2 infected hACE2 mice treated orally, post-infection, with the NLRP3 inhibitory drug MCC950, have significantly reduced microglial inflammasome activation, and increased survival in comparison with untreated SARS-CoV-2 infected mice.
“We found it [the drug] successfully blocked the inflammatory pathway activated by COVID-19, essentially putting out the fire,” 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,” he added.
The authors write that, “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.”
Woodruff said while the similarity between how COVID-19 and dementia diseases affect the brain was concerning, it also suggested a possible treatment was already in existence.
“Further research is needed,” he added, “but this is potentially a new approach to treating a virus that could otherwise have untold long-term health ramifications.”
