An autoimmune response causes transmissible spongiform encephalopathies

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.