It is known that coronavirus infection can cause various, including neurological, chronic conditions. In recent years, more and more studies have been published showing an increased risk of Parkinson's disease in people who have recovered from COVID-19. An important factor in neurodegenerative processes in the brain are NLRP3 microglial inflammasomes, multiprotein complexes that are responsible for the production of cytokines that promote inflammatory reactions.

To test whether COVID-19 could promote NLRP3 activation, the scientists used a preclinical model: transgenic mice expressing human angiotensin-converting enzyme 2 (hACE2). ACE2 is a membrane protein located on the cell surface and is the entry point for SARS-CoV-2. ACE2 is produced by many cell types, including not only respiratory tract cells, but also brain neurons and microglia (macrophages of the central nervous system), making them potentially vulnerable to infection. SARS-CoV-2 binds to ACE2 of human cells via the viral spike protein S.

It turned out that the virus actually penetrated the rodent brain, where it promoted the activation of pro-inflammatory pathways involving NLRP3. A laboratory model of microglia additionally grown from human monocytes demonstrated that SARS-CoV-2 viral particles are able to bind to and enter cells, which directly causes strong inflammatory responses. Even a purified S-protein, interacting with angiotensin-converting enzyme 2, activated the NLRP3 inflammasome in microglial cells.