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An autoimmune response causes transmissible spongiform encephalopathies
1Bank Farm Carlton, Nuneaton, UK. janie.bankfarm@pipemedia.co.uk
Abstract:
Misfolded prion protein (PrP) is generally accepted as causing transmissible spongiform encephalopathies (TSEs) by aligning alongside normal host prion protein and inducing it to change to the misfolded configuration. This paper disputes this theory, and proposes that, rather than causing TSEs, misfolded PrP is the result of an autoimmune response to the host PrP, a component both of nerve cells and of lymphocytes. Autoimmunity is initiated by detachment of the phosphotidylinositol glycolipid anchor as a result of exposure to organophosphate pesticides. Once PrP is detached, antibodies are mobilized against it. In some individuals, point mutations, like the codon 129 met-val substitution, have evolved as a self-defence mechanism, causing a change in PrP to the misfolded, protease-resistant form seen in TSEs. Increased PrP production, both in response to nerve damage, and as a component of lymphocytes stimulated to proliferate in response to PrP, produces a positive feedback mechanism, resulting in symptoms of brain destruction.
Insights
Misfolded prion protein (PrP) is not the cause of transmissible spongiform encephalopathies (TSEs). Instead, misfolded PrP results from an autoimmune response triggered by organophosphate pesticides, leading to TSE symptoms.
Area of Science:
- Neuroscience
- Immunology
- Toxicology
Background:
- Transmissible spongiform encephalopathies (TSEs) are linked to misfolded prion protein (PrP).
- The prevailing theory suggests misfolded PrP induces normal PrP into a misfolded state, causing disease.
- This view is challenged by an alternative hypothesis.
Purpose of the Study:
- To dispute the conventional theory of prion protein (PrP) in transmissible spongiform encephalopathies (TSEs).
- To propose an alternative autoimmune-driven mechanism for misfolded PrP formation and TSE pathogenesis.
Main Methods:
- The study presents a theoretical dispute of the established prion disease mechanism.
- It proposes a novel pathway involving autoimmune responses to host prion protein (PrP).
- Environmental factors like organophosphate pesticides are implicated as triggers.
Main Results:
- Misfolded prion protein (PrP) is proposed to be a result, not a cause, of transmissible spongiform encephalopathies (TSEs).
- Autoimmunity against host PrP is initiated by organophosphate pesticide exposure, detaching the glycolipid anchor.
- Point mutations, such as codon 129, may represent a self-defense mechanism leading to misfolded PrP.
- Increased PrP production creates a positive feedback loop, exacerbating neurological damage.
Conclusions:
- The conventional prion protein (PrP) theory for transmissible spongiform encephalopathies (TSEs) is contested.
- An autoimmune response, potentially triggered by organophosphate pesticides, is proposed as the primary driver of TSEs.
- Genetic factors and increased PrP production contribute to disease progression.