@article{d680c2f25afe49509e1c05b805ff2604,
title = "Selective positive modulator of calcium-activated potassium channels exerts beneficial effects in a mouse model of spinocerebellar ataxia type 2",
abstract = "Spinocerebellar ataxia type 2 (SCA2) is a neurodegenerative disorder caused by a polyglutamine expansion within the Ataxin-2 (Atxn2) protein. Purkinje cells (PC) of the cerebellum fire irregularly and eventually die in SCA2. We show here that the type 2 small conductance calcium-activated potassium channel (SK2) play a key role in control of normal PC activity. Using cerebellar slices from transgenic SCA2 mice we demonstrate that SK channel modulators restore regular pacemaker activity of SCA2 PCs. Furthermore, we also show that oral delivery of a more selective positive modulator of SK2/3 channels (NS13001) alleviates behavioral and neuropathological phenotypes of aging SCA2 transgenic mice. We conclude that SK2 channels constitute a therapeutic target for SCA2 treatment and that the developed selective SK2/3 modulator NS13001 holds promise as a potential therapeutic agent for treatment of SCA2 and possibly other cerebellar ataxias.",
author = "Kasumu, {Adebimpe W.} and Charlotte Hougaard and Frederik Rode and Jacobsen, {Thomas A.} and Sabatier, {Jean Marc} and Eriksen, {Birgitte L.} and Dorte Strob{\ae}k and Xia Liang and Polina Egorova and Dasha Vorontsova and Palle Christophersen and Ronn, {Lars Christian B} and Ilya Bezprozvanny",
note = "Funding Information: We thank Leah Taylor for administrative assistance. Vibeke Meyland-Smith and Susanne Kalf Hansen are greatly acknowledged for their help with patch clamp experiments and preparation of cerebellar slices. Lise Lauenborg is acknowledged for help with the synthesis of CyPPA and NS13001. Dr. Nicolas Andreotti is thanked for his help with the synthesis of LeiDab-7. A.W.K. is a Howard Hughes Medical Institute Med into Grad scholar. I.B. is a holder of the Carl J. and Hortense M. Thomsen Chair in Alzheimer{\textquoteright}s Disease Research. This study is supported in part by a contract with Neurosearch A/S (to P.C., L.C.B.R., and I.B.), by the NIH Grants R01NS056224, R01NS38082 and R01NS074376 (to I.B.), Welch Foundation grant I-1754 (to I.B.), and by the contract with the Russian Ministry of Science 14.740.11.0924 (to I.B.). С.H., F.R., T.A.J., B.L.E., D.S., P.C., and L.C.B.R. are employees and shareholders of Neurosearch A/S. ",
year = "2012",
month = oct,
day = "26",
doi = "10.1016/j.chembiol.2012.07.013",
language = "English (US)",
volume = "19",
pages = "1340--1353",
journal = "Cell Chemical Biology",
issn = "2451-9448",
publisher = "Elsevier Inc.",
number = "10",
}