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Properties of scyllo–inositol as a therapeutic treatment of AD-like pathology

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Abstract

Inositol is a simple polyol with eight naturally occurring stereoisomers. myo–Inositol, D-chiro– and epi–inositol have been examined as potential therapeutic agents for various diseases, with favorable results, but treatment with scyllo–inositol has not been previously investigated. Our laboratory has shown that scyllo–inositol inhibits cognitive deficits in TgCRND8 mice and significantly ameliorates disease pathology, suggesting it might be effective in treating Alzheimer’s disease (AD). In this paper, we show that scyllo–inositol has a sustained ability to treat animals at advanced stages of AD-like pathology. Significant decreases in insoluble Aβ40, Aβ42, and plaque accumulation were observed in the brains of treated versus untreated TgCRND8 mice. The growth of plaques of all sizes was inhibited by scyllo–inositol administration. To demonstrate that the scyllo–inositol effects were within the CNS, gas chromatography/mass spectrometry was used to examine myo– and scyllo–inositol concentrations after oral administration. Further, we examined how closely scyllo– and myo–inositol are inter-regulated in the CNS and whether scyllo–inositol, if elevated within the CNS, would incorporate into phosphatidylinositol lipids. Cerebral spinal fluid levels of scyllo–inositol increased after scyllo–inositol treatment but not myo–inositol treatment. scyllo-Inositol treatment also caused increased levels of scyllo–inositol in the brain. We further show that scyllo–inositol, even at elevated levels, does not incorporate into the phosphatidylinositol family of lipids. These combined results demonstrate that scyllo–inositol accumulates within the CNS up to tenfold endogenous levels and does not interfere with phosphatidylinositol lipid production.

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Acknowledgment

The authors would like to thank the staff at the Analest Center, Chemistry Department University of Toronto, for the advice on the GC/MS and the staff at the Division of Comparative Medicine at the University of Toronto. The authors acknowledge support from the Ontario Alzheimer’s Society (J.M.), Canadian Institutes of Health Research (J.M.), Natural Science and Engineering Research Council of Canada (J.M.), Ontario Graduate Scholarship (D.F.), and Scottish Rite Charitable Foundation Graduate Fellowship (D.F.).

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Authors and Affiliations

  1. Centre for Research in Neurodegenerative Diseases, University of Toronto, 6 Queen’s Park Crescent West, Toronto, Ontario, M5S 3H2, Canada

    Daniela Fenili, Mary Brown, Rebecca Rappaport & JoAnne McLaurin

  2. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada

    Daniela Fenili & JoAnne McLaurin

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  1. Daniela Fenili
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Correspondence to JoAnne McLaurin.

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Fenili, D., Brown, M., Rappaport, R. et al. Properties of scyllo–inositol as a therapeutic treatment of AD-like pathology. J Mol Med 85, 603–611 (2007). https://doi.org/10.1007/s00109-007-0156-7

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  • DOI: https://doi.org/10.1007/s00109-007-0156-7

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