scyllo-Inositol

scyllo-Inositol is a stereoisomer of inositol. It induces a structural transition in amyloid-β (1-42) (Aβ42), but not Aβ40, from a random coil to β-sheet structure but prevents Aβ42 fibril formation in cell-free assays.¹ scyllo-Inositol reduces Aβ40- and Aβ42-induced decreases in the survival of PC12 cells. It reduces increases in soluble and insoluble brain Aβ40 and Aβ42 levels in four- and six-month-old mice in the TgCRND8 model of Alzheimer’s disease when administered starting at six weeks of age, which is prior to the onset of increased Aβ levels and spatial learning deficits.² It also reduces increases in insoluble brain Aβ40 and Aβ42 levels in six-month-old mice when administered starting at five months of age when the neuropathological and learning deficits are already established. scyllo-Inositol improves established spatial learning and memory deficits in the Morris water maze when compared with TgCRND8 control and non-transgenic littermate control mice. It also improves survival of TgCRND8 mice.

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1. McLaurin, J., Golomb, R., Jurewicz, A., et al. Inositol stereoisomers stabilize an oligomeric aggregate of Alzheimer amyloid β peptide and inhibit Αβ-induced toxicity. The Journal of Biological Chemisty 275(24), 18495-18502 (2000).

2. McLaurin, J., Kierstead, M.E., Brown, M.E., et al. Cyclohexanehexol inhibitors of Aβ aggregation prevent and reverse Alzheimer phenotype in a mouse model. Nat. Med. 12(7), 801-808 (2006).