The sigma-1 receptor mediates the beneficial effects of pridopidine in a mouse model of Huntington disease

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• 作者：Daniel Ryskamp^a ; ^{Daniel.Ryskamp@UTSouthwestern.edu} ; Jun Wu^a ; ^{Jun.Wu@UTSouthwestern.edu} ; Michal Geva^b ; ^{Michal.Geva@teva.co.il} ; Rebecca Kusko^c ; ^{BKusko@immuneering.com} ; Iris Grossman^b ; ^{Iris.Grossman@teva.co.il} ; Michael Hayden^b ; ^{Michael.Hayden@teva.co.il} ; Ilya Bezprozvanny^a ; ^{Ilya.Bezprozvanny@UTSouthwestern.edu}
• 关键词：HD ; Huntington disease ; Htt ; Huntingtin ; MSN ; medium spiny neuron ; S1R ; sigma-1 receptor ; ER ; endoplasmic reticulum ; YAC128 ; yeast artificial chromosome 128Q expansion mice ; 3-PPP ; R(+)-3-(3-Hydroxyphenyl)-N-propylpiperidine hydrochloride ; SOC ; store-operated calcium current ; MAM ; mitochondrial-associated membrane ; gLacZ ; guideRNA targeting the bacterial β-galactosidase gene ; gS1R ; guideRNA targeting the mouse S1R gene ; MEF ; mouse embryonic fibroblasts ; DHPG ; (S)-3 ; 5-dihydroxyphenylglycine ; IO
• 刊名：Neurobiology of Disease
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：97
• 期：part_PA
• 页码：46-59
• 全文大小：1602 K
• 卷排序：97

文摘

Striatal S1R is upregulated in both mice and patients with advanced but not early HD. Pridopidine stabilizes MSN spines in aging YAC128 corticostriatal co-cultures via S1R. Pridopidine normalizes synaptic and ER Ca2 + homeostasis in YAC128 MSNs. Pridopidine upregulates calbindin and homer1a, which are downregulated in HD models. The therapeutic effects of pridopidine in HD treatment are likely mediated by the S1R.