Endotoxin/LPS-driven inflammation can cause “Mad Cow” disease by itself, no prions needed
-
Yet another mysterious and deadly condition may turn out to be nothing more than endotoxin/LPS overload in disguise. For decades, we have been told that the dreaded so-called “Mad Cow” disease (also known as BSE) can only be caused by a misfolded, infections proteins that accumulate in the brain and cause irreversible damage that is invariably lethal. The study below pours cold water on those claims and calls for a complete revamping of the hypothesis behind the BSE condition. The study demonstrated that the administration of endotoxin/LPS by itself was enough to reproduce all features of the disease (except the infectious aspects), with the same lethality as the one seen in the experimental groups that received injections with the actual infectious, misfolded, BSE-causing prions. When endotoxin/LPS as administered together with the prion injections, the effects were synergistic. As the authors state, inflammation may be the original driver of BSE pathology, with the prions being a late effect of the already established systemic inflammatory state caused by endotoxin/LPS. And last but not least, the fact that endotoxin/LPS injections caused beta-amyloid accumulation and cognitive deficits strongly suggests that another incurable, progressive and lethal brain condition – Alzheimer’s Disease – is also endotoxin/LPS/inflammation-driven.
https://doi.org/10.3390/ijms26136245
https://www.sciencealert.com/prion-like-brain-damage-can-occur-without-infectious-prions-study-finds
“…We may have been overestimating the role of a pathological class of misfolded protein in neurodegenerative disease. Called prions, these molecules are responsible for conditions such as bovine spongiform encephalopathy or ‘mad cow disease’, chronic wasting disease in deer, and Creutzfeldt-Jakob disease in humans. A new study in mice has found that some of the hallmarks of prion disease in brain tissue – such as the appearance of sponge-like holes, scarring, and accumulation of amyloid plaques – can develop even in the complete absence of prions in their infectious configuration….This finding suggests we have overlooked some of the mechanisms that contribute to prion diseases, and in some cases, even mistaken the underlying cause. It also has implications for prion-like conditions such as Alzheimer’s, Parkinson’s, and ALS, in which misfolded proteins are central to irreversible brain damage.”
“…Other emerging evidence suggests that a bacterial endotoxin called lipopolysaccharide (LPS), found on the outer membranes of some bacteria, can accelerate prion disease by inducing protease resistance in prion proteins. It also activates the host immune system’s inflammatory response, further contributing to neurodegeneration.”
“…The group that was given just the misfolded, non-infectious PrP alone developed the spongiform brain damage and scarring, but not the protease-resistant PrP that defines infectious prions. Meanwhile, the LPS-only group developed amyloid plaques, spongiform damage, and a high 40 percent mortality rate – but again, no protease resistance. Combining LPS with the non-infectious PrP misfold did not increase lethality, but holes in the brains of mice in this group did grow larger. Finally, combining the prion with LPS dramatically accelerated the course of the disease. All of the mice in this group died within 200 days.”
“…This fundamentally challenges the prevailing theory that these types of brain diseases are only about prions or similar misfolded proteins,” Ametaj says. The results suggest that, in at least some prion diseases, the host may first be weakened by inflammation before the protein misfolding that leads to prion formation – that prion disease may not actually start with prions, but with inflammation, or the non-infectious, misfolded PrP.
“