@article{d9a139dbdd754d47a07ab29f60191401,
title = "Neuronal store-operated calcium entry pathway as a novel therapeutic target for Huntington's disease treatment",
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 (Ca2+) 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.",
author = "Jun Wu and Shih, {Hsin Pei} and Vladimir Vigont and Lori Hrdlicka and Len Diggins and Carol Singh and Matt Mahoney and Richard Chesworth and Gideon Shapiro and Olga Zimina and Xuesong Chen and Qingqing Wu and Lyubov Glushankova and Michael Ahlijanian and Gerhard Koenig and Mozhayeva, {Galina N.} and Elena Kaznacheyeva and Ilya Bezprozvanny",
note = "Funding Information: We thank Juan Botas (Baylor University) for generously providing us transgenic mhtt128 HD flies that were used to generate the stocks in this study, Leonidas Tsiokas (University of Oklahoma Health Sciences Center) for a gift of human TRPC1-RNAi plasmid, Yuemei Li and Huarui Liu for help with maintaining the YAC128 mouse colony and genotyping, Leah Benson for administrative assistance, and Tie-Shan Tang for helpful advice. I.B. is a holder of Carl J. and Hortense M. Thomsen chair in Alzheimer's disease research. The study was supported by EnVivo Inc, CHDI foundation, and the NINDS (R01 NS056224 to I.B.), the Program of Ministry of Science and Education GCs N 14.740.11.0924 (I.B. and E.K.) and N P332 (E.K.), the program of Molecular and Cellular Biology RAS (EK), and Russian Basic Research Foundation 10-04-00956 (E.K.). H.-P.S., L.H., L.D., C.S., M.M., R.C., G.S., M.A., and G.K. are current or former employees and shareholders of EnVivo Inc. This work was supported in part by a contract with EnVivo Inc. I.B. was a paid consultant of EnVivo Inc. ",
year = "2011",
month = jun,
day = "24",
doi = "10.1016/j.chembiol.2011.04.012",
language = "English (US)",
volume = "18",
pages = "777--793",
journal = "Cell Chemical Biology",
issn = "2451-9448",
publisher = "Elsevier Inc.",
number = "6",
}