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Citation
Wu, J., Shih, H.P., Vigont, V., Hrdlicka, L., Diggins, L., Singh, C., Mahoney, M., Chesworth, R., Shapiro, G., Zimina, O., Chen, X., Wu, Q., Glushankova, L., Ahlijanian, M., Koenig, G., Mozhayeva, G.N., Kaznacheyeva, E., Bezprozvanny, I. (2011). Neuronal Store-Operated Calcium Entry Pathway as a Novel Therapeutic Target for Huntington's Disease Treatment.  Chem. Biol. 18(6): 777--793.
FlyBase ID
FBrf0214007
Publication Type
Research paper
Abstract

Huntington's disease (HD) is a neurodegenerative disorder caused by a polyglutamine expansion within Huntingtin (Htt) protein. In the phenotypic screen we identified a class of quinazoline-derived compounds that delayed a progression of a motor phenotype in transgenic Drosophila HD flies. We found that the store-operated calcium (Ca(2+)) entry (SOC) pathway activity is enhanced in neuronal cells expressing mutant Htt and that the identified compounds inhibit SOC pathway in HD neurons. The same compounds exerted neuroprotective effects in glutamate-toxicity assays with YAC128 medium spiny neurons primary cultures. We demonstrated a key role of TRPC1 channels in supporting SOC pathway in HD neurons. We concluded that the TRPC1-mediated neuronal SOC pathway constitutes a novel target for HD treatment and that the identified compounds represent a novel class of therapeutic agents for treatment of HD and possibly other neurodegenerative disorders.

PubMed ID
PubMed Central ID
PMC3124661 (PMC) (EuropePMC)
Associated Information
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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Chem. Biol.
    Title
    Chemistry & Biology
    Publication Year
    1994-
    ISBN/ISSN
    1879-1301 1074-5521
    Data From Reference
    Alleles (2)
    Genes (2)
    Human Disease Models (1)
    Insertions (1)
    Transgenic Constructs (1)