Cholecystokinin Activation of Cholecystokinin 1 Receptors: a Purkinje Cell Neuroprotective Pathway.
Cholecystokinin Activation of Cholecystokinin 1 Receptors: a Purkinje Cell Neuroprotective Pathway.
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DOI：
10.1007/s12311-022-01428-x
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发表时间：
2023-08
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影响因子：
--
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这是小脑和共济失调研究学会 2021 年会议上虚拟演示的摘要，https://www.meetings.be/SRCA2021/，其中介绍了 CCK-CCK1R 通路治疗涉及浦肯野细胞变性的疾病的治疗潜力。脊髓小脑性共济失调 1 型 (SCA1) 是一组近 50 种以小脑浦肯野细胞变性为特征的遗传性疾病之一。 SCA1 Pcp2-ATXN1[30Q]D776 小鼠模型表现出共济失调，即浦肯野细胞功能障碍，但缺乏进行性浦肯野细胞变性。 RNA-seq 显示 Pcp2-ATXN1[30Q]D776 小鼠小脑中胆囊收缩素 (CCK) 的表达增加。重要的是，Pcp2-ATXN1[30Q]D776 小鼠中 Cck1 受体 (CCK1R) 的缺失会导致进行性退行性疾病，伴有浦肯野细胞丢失。对 Pcp2-AXTN1[82Q] 小鼠施用 CCK1R 激动剂可减少浦肯野细胞病理学和相关的运动表现缺陷。此外，给予 CCK1R 激动剂可改善 Pcp2-ATXN2[127Q] SCA2 小鼠的运动表现。此外，CCK1R 激活纠正了 mTORC1 信号传导并改善了 AXTN1[82Q] 和 ATXN2[127Q] 小鼠小脑中钙结合蛋白的表达。这些结果支持 Cck-Cck1R 通路是治疗涉及浦肯野神经元变性的疾病的潜在治疗靶点。
This is a summary of the virtual presentation given at the 2021 meeting of the Society for Research on the Cerebellum and Ataxias, https://www.meetings.be/SRCA2021/, where the therapeutic potential of the CCK-CCK1R pathway for treating diseases involving Purkinje cell degeneration was presented. Spinocerebellar ataxia type 1 (SCA1) is one of a group of almost 50 genetic diseases characterized by the degeneration of cerebellar Purkinje cells. The SCA1 Pcp2-ATXN1[30Q]D776 mouse model displays ataxia, i.e. Purkinje cell dysfunction, but lacks progressive Purkinje cell degeneration. RNA-seq revealed increased expression of cholecystokinin (CCK) in cerebella of Pcp2-ATXN1[30Q]D776 mice. Importantly, the absence of Cck1 receptor (CCK1R) in Pcp2-ATXN1[30Q]D776 mice conferred a progressive degenerative disease with Purkinje cell loss. Administration of a CCK1R agonist to Pcp2-AXTN1[82Q] mice reduced Purkinje cell pathology and associated deficits in motor performance. In addition, administration of the CCK1R agonist improved motor performance of Pcp2-ATXN2[127Q] SCA2 mice. Furthermore, CCK1R activation corrected mTORC1 signaling and improved the expression of calbindin in the cerebella of AXTN1[82Q] and ATXN2[127Q] mice. These results support the Cck-Cck1R pathway is a potential therapeutic target for the treatment of diseases involving Purkinje neuron degeneration.
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影响因子：
16.2
作者：
Ingram M;Wozniak EAL;Duvick L;Yang R;Bergmann P;Carson R;O'Callaghan B;Zoghbi HY;Henzler C;Orr HT
通讯作者：
Orr HT
DOI：
10.1038/nrn.2017.92
发表时间：
2017-10
期刊：
Nature reviews. Neuroscience
影响因子：
--
作者：
Paulson HL;Shakkottai VG;Clark HB;Orr HT
通讯作者：
Orr HT
影响因子：
29
作者：
Bettencourt, Conceicao;Ryten, Mina;Forabosco, Paola;Schorge, Stephanie;Hersheson, Joshua;Hardy, John;Houlden, Henry
通讯作者：
Houlden, Henry
DOI：
10.1136/jnnp-2014-308421
发表时间：
2015-05
期刊：
Journal of neurology, neurosurgery, and psychiatry
影响因子：
--
作者：
Hekman KE;Gomez CM
通讯作者：
Gomez CM
影响因子：
5.5
作者：
Schmidt, H;Stiefel, KM;Eilers, J
通讯作者：
Eilers, J