American Scientists Alarmed as SARS-CoV-2 Spike Protein Found to Accelerate Brain Cell Aging via TLR7 Pathway
Nikhil Prasad Fact checked by:Thailand Medical News Team Nov 02, 2025 6 hours, 31 minutes ago
Medical News: SARS-CoV-2 Spike Protein Found to Damage Brain Cells and Cause Premature Aging
Scientists from the University of North Dakota School of Medicine and Health Sciences have uncovered a new mechanism explaining how the SARS-CoV-2 virus could be driving long-term brain damage and neuropsychiatric issues in COVID-19 survivors. The research team, led by Dr. Xuesong Chen, found that the spike protein’s S1 subunit—the same portion responsible for attaching to human cells—can trigger aging-like changes in brain cells called astrocytes. These findings provide a critical clue to understanding why millions of people with long COVID continue to experience brain fog, anxiety, depression, and memory problems long after infection.
American Scientists Alarmed as SARS-CoV-2 Spike Protein Found to Accelerate Brain Cell Aging via TLR7 Pathway
How the Spike Protein Affects the Brain
In this
Medical News report, the study reveals that the spike S1 protein can enter brain cells and cause a malfunction in a part of the cell known as the endolysosome—an internal recycling and waste-removal structure. When this system becomes damaged, the cell begins to show signs of aging, including the release of inflammatory chemicals and the halt of normal cell division. This process, known as cellular senescence, can create a toxic environment in the brain and promote inflammation, similar to what is seen in conditions such as Alzheimer’s and Parkinson’s disease.
The Role of the TLR7 Pathway
The research team discovered that this damaging effect of the S1 protein depends on a key protein called Toll-like receptor 7 (TLR7), which normally detects viral RNA inside cells. When the spike protein binds to TLR7, it activates a stress-signaling route known as p38 MAPK, setting off a chain reaction that damages cell membranes, releases inflammatory molecules such as IL-6, and pushes astrocytes into a senescent state. Blocking the TLR7 pathway or the p38 MAPK signal was shown to stop these harmful effects, suggesting that these molecular pathways might be potential therapeutic targets for long COVID brain symptoms.
Key Laboratory Findings
The researchers found that the multibasic motif—a specific molecular structure in the spike protein—was essential for this harmful interaction. When they used a modified version of the S1 protein without this motif, it could still enter the brain cells but failed to cause damage or trigger inflammation. They also observed that the treated cells released higher levels of galectin-3, cathepsin B, and IL-6, all of which are associated with chronic inflammation and brain injury.
Further experiments showed that the spike protein did not directly kill the astrocytes but instead caused them to remain alive in a dysfunctional, inflammatory state. This kind of persistent inflammation is believed to underlie neuro-PASC, or neurological post-acute sequelae of COVID-19, which affects memory, focus, and mood regulation in long COV
ID patients.
Implications for Long COVID and Neurodegeneration
The findings suggest that even after the virus itself is cleared from the body, remnants of the spike protein can remain in the brain and continue to harm cells. Over time, this process could lead to accelerated brain aging, neuroinflammation, and possibly contribute to neurodegenerative disorders. Researchers propose that drugs designed to block the TLR7 receptor or p38 MAPK signaling could be explored to prevent or reverse such effects in long COVID patients.
Summary
This groundbreaking discovery sheds light on how the SARS-CoV-2 spike protein can set off a cascade of inflammation and premature cellular aging in the brain. By identifying TLR7 and the p38 MAPK pathway as central players in this process, the study opens new possibilities for therapeutic interventions targeting the lingering neurological effects of COVID-19. The persistence of the spike protein in the brain could explain why some patients suffer long-term symptoms despite testing negative for the virus.
The study findings were published in the peer reviewed Journal of Neuroinflammation.
https://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-025-03586-1
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