Mad cow disease: A new culprit beyond prions

Recent research  by  scientists challenges the belief that mad cow disease is caused only by misfolded proteins—a discovery that sheds new light on the devastating outbreak in the United Kingdom 40 years ago and provides new hope for prevention. 

The study, published in the International Journal of Molecular Sciences, shows for the first time that such prion-like brain diseases can be triggered without the presence of infectious prions. Prion disease occurs when normal proteins in the brain misfold into infectious, abnormal proteins. 

Instead, chronic inflammation caused by a powerful bacterial endotoxin called lipopolysaccharide (LPS) was identified as a culprit that can independently trigger brain damage resembling prion disease. 

This fundamentally challenges the prevailing theory that these types of brain diseases are only about prions or similar misfolded proteins.

  The research revealed more of a multifaceted process behind that neurodegeneration, showing that inflammation weakens the brain's defenses first, overwhelming cells. Proteins could then start misfolding and the immune system over-reacts, causing more damage. 

All three processes feed into each other, which means we need to target inflammation and immune health, not just the misfolded proteins, say the researchers. 

The discovery suggests that endotoxins in the animal-derived feed offered to cattle may have contributed to the bovine spongiform encephalopathy (BSE), or mad cow disease, crises in the United Kingdom .

The research also showed that when an actual prion disease such as BSE is present, inflammation caused by LPS dramatically worsens damage to the brain, resulting in 100% mortality within 200 days of infection. 

Seyed Ali Goldansaz et al, Lipopolysaccharide and Recombinant Prion Protein Induce Distinct Neurodegenerative Pathologies in FVB/N Mice, International Journal of Molecular Sciences (2025). DOI: 10.3390/ijms26136245