Autor: |
Chaves G; Biomolecular Engineering Department, University of California Santa Cruz, 1156 High Street, Santa Cruz, CA 95064, USA., Özel RE; Biomolecular Engineering Department, University of California Santa Cruz, 1156 High Street, Santa Cruz, CA 95064, USA., Rao NV; Biomolecular Engineering Department, University of California Santa Cruz, 1156 High Street, Santa Cruz, CA 95064, USA., Hadiprodjo H; Biomolecular Engineering Department, University of California Santa Cruz, 1156 High Street, Santa Cruz, CA 95064, USA., Costa YD; Biomolecular Engineering Department, University of California Santa Cruz, 1156 High Street, Santa Cruz, CA 95064, USA., Tokuno Z; Biomolecular Engineering Department, University of California Santa Cruz, 1156 High Street, Santa Cruz, CA 95064, USA., Pourmand N; Biomolecular Engineering Department, University of California Santa Cruz, 1156 High Street, Santa Cruz, CA 95064, USA. |
Abstrakt: |
Huntington's Disease (HD) is a neurodegenerative disorder caused by an expansion in a CAG-tri-nucleotide repeat that introduces a poly-glutamine stretch into the huntingtin protein (mHTT). Mutant huntingtin (mHTT) has been associated with several phenotypes including mood disorders and depression. Additionally, HD patients are known to be more susceptible to type II diabetes mellitus (T2DM), and HD mice model develops diabetes. However, the mechanism and pathways that link Huntington's disease and diabetes have not been well established. Understanding the underlying mechanisms can reveal potential targets for drug development in HD. In this study, we investigated the transcriptome of mHTT cell populations alongside intracellular glucose measurements using a functionalized nanopipette. Several genes related to glucose uptake and glucose homeostasis are affected. We observed changes in intracellular glucose concentrations and identified altered transcript levels of certain genes including Sorcs1, Hh-II and Vldlr . Our data suggest that these can be used as markers for HD progression. Sorcs1 may not only have a role in glucose metabolism and trafficking but also in glutamatergic pathways affecting trafficking of synaptic components. |