Manganese chelation therapy extends survival in a mouse model of M1000 prion disease.

摘要: J. Neurochem. (2010) 114, 440–451. Abstract Previous in vitro and vivo investigations have suggested manganese (Mn2+) may play a role pathogenesis through facilitating refolding of the normal cellular form prion protein into protease resistant, pathogenic isoforms (PrPSc), as well subsequent promotion higher order aggregation these abnormal conformers. To further explore Mn2+ pathogenesis, we undertook number studies, including an assessment disease modifying effects chelation therapy well-characterized mouse model disease. The di-sodium, calcium derivative chelator, cyclohexanediaminetetraacetic acid (Na2CaCDTA), was administered intraperitoneally to mice inoculated intra-cerebrally with either high or low-dose inocula, treatment beginning early (shortly after inoculation) late (at usual mid-survival point untreated mice). Analyses by inductively coupled plasma-mass spectrometry demonstrated brain levels were selectively reduced up 50% treated compared controls, copper, iron, zinc cobalt unchanged. In high-dose none groups displayed increase survival although western blot analyses intensively showed PrPSc levels; infected using inocula however, significant prolongation (p = 0.002). Although our findings support for disease, studies are required more precisely delineate extent involvement.