Selective Positive Modulator of Calcium-Activated Potassium Channels Exerts Beneficial Effects in a Mouse Model of Spinocerebellar Ataxia Type 2
作者： Adebimpe W. Kasumu , Charlotte Hougaard , Frederik Rode , Thomas A. Jacobsen , Jean Marc Sabatier
DOI: 10.1016/J.CHEMBIOL.2012.07.013
关键词:
摘要: Spinocerebellar ataxia type 2 (SCA2) is a neurodegenerative disorder caused by polyglutamine expansion within the Ataxin-2 (Atxn2) protein. Purkinje cells (PC) of cerebellum fire irregularly and eventually die in SCA2. We show here that small conductance calcium-activated potassium channel (SK2) play key role control normal PC activity. Using cerebellar slices from transgenic SCA2 mice we demonstrate SK modulators restore regular pacemaker activity PCs. Furthermore, also oral delivery more selective positive modulator SK2/3 channels (NS13001) alleviates behavioral neuropathological phenotypes aging mice. conclude SK2 constitute therapeutic target for treatment developed NS13001 holds promise as potential agent possibly other ataxias.
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