Year: 2009
Type: article
Abstract: One challenge to designing drugs for targeting CNS diseases is to develop compounds that when given orally, cross the blood-brain barrier to reach their target sites in the brain. One design strategy is to develop drugs that can cross into the brain using a known transport system. myo-Inositol is able to cross into the brain using the inositol transporters, of which there are three: one hydrogen/myo-inositol cotransporter (HMIT) and two sodium/myo-inositol cotransporters (SMIT1, SMIT2). Our laboratory has previously shown that scyllo-inositol, ELND005, is able to both prevent and reverse Alzheimer's disease pathology in the TgCRND8 mouse model of Alzheimer's disease. We have also shown, using gas chromatography/mass spectrometry, that ad libitum treatment of mice with scyllo-inositol results in a significant increase in the brain levels of scyllo-inositol in both TgCRND8 and non-Tg littermates (Fenili et al, 2007, J Mol Med). Competitive transport assays have been developed to examine the minimal binding requirements for transport by the three known inositol transporters in astrocytic and neural cell lines. Inositol, simple sugars and related compounds, 20 in total, were used to define the structural features required for active transport. Further the relative expression of the transporters as a function of age and disease progression was analyzed in the cortex, hippocampus, septum and cerebellum using QPCR. Across all brain regions analyzed the expression level of the transporters were HMIT > SMIT1 > SMIT2. This result did not vary with age or disease phenotype. All three inositol transporters are expressed in the brain, with a similar pattern of expression being observed regardless of brain region.
Source: Alzheimer s & Dementia
Authors: Daniela Fenili, Mark Nitz, JoAnne McLaurin
Institution: University of Toronto
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W1998726312