Prion protein fragment 106-126 is the best known synthetic model of prion neurotoxicity. Reported in Nature as a neurotoxic fragment of the prion protein, it reproduces in culture the neuronal death characteristic of prion disease without requiring infectious material, which is why it became a standard tool: it allows mechanism to be studied under ordinary laboratory containment. The supplied sequence includes the hydrophobic AGAAAAGA palindromic stretch that drives its self-assembly, and the peptide forms amyloid fibrils whose core structure has been determined. A central and much-discussed finding is that toxicity and fibril formation can be separated: the fragment induces p38 MAP kinase-dependent apoptosis in SH-SY5Y neuroblastoma cells independently of amyloid fibril formation, meaning the fibrillar end state is not required for cell death. Work using poly(ADP-ribose) immunostaining characterised the apoptotic response, and further studies reported that toxicity is independent of cellular prion protein expression level and is not mediated by abnormal PrP species. Those findings shape how the peptide should be used. Because aggregation state and toxicity are dissociable, preparation history matters: freshly dissolved and pre-aggregated material are not equivalent, and results are difficult to interpret without characterising the state of the peptide actually applied. Reports across laboratories differ partly for this reason. | 