biostudies-literatureEmendato AEuropean Research Council1704https://www.ebi.ac.uk/biostudies/studies/S-EPMC12657908biostudies-literatureUnknown8(1)The misfolding of the human prion protein (hPrP) and the consequent self-assembly into insoluble amyloid fibrils are associated with neurodegenerative diseases known as transmissible spongiform encephalopathies (TSEs). In this study, we investigated the stability and aggregation behaviour of the folded C-terminal domain of hPrP (hPrP^C_125-230) and observed that, under specific experimental conditions, this region of the protein rapidly aggregates into round-shaped oligomers. The isolated oligomers exhibited hallmarks properties of amyloid aggregates, including a β-sheet-rich structure, enhanced hydrophobic exposure, and Thioflavin T (ThT)-induced fluorescence. When incubated with neural precursor cells these hPrP oligomers, unlike monomeric species, induced mitochondriCommunications biologyStructural and cellular properties of human prion protein oligomers.PMC12657908BioDisOrder - 819644Parisi SZizolfi MCMansueto SPeltrini RDe Simone AEmendato ADivisato GGiannino EfalseStructural and cellular properties of human prion protein oligomers.The misfolding of the human prion protein (hPrP) and the consequent self-assembly into insoluble amyloid fibrils are associated with neurodegenerative diseases known as transmissible spongiform encephalopathies (TSEs). In this study, we investigated the stability and aggregation behaviour of the folded C-terminal domain of hPrP (hPrP^C_125-230) and observed that, under specific experimental conditions, this region of the protein rapidly aggregates into round-shaped oligomers. The isolated oligomers exhibited hallmarks properties of amyloid aggregates, including a β-sheet-rich structure, enhanced hydrophobic exposure, and Thioflavin T (ThT)-induced fluorescence. When incubated with neural precursor cells these hPrP oligomers, unlike monomeric species, induced mitochondri2025-01-01T00:00:00Z2025 Nov2026-06-07T04:32:59.83Z2026-06-07T03:06:56.548ZS-EPMC126579084129903410.1038/s42003-025-09105-5