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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 <jats:italic>Pcp2-ATXN1[30Q]D776<\/jats:italic> 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 <jats:italic>Pcp2-ATXN1[30Q]D776<\/jats:italic> mice. Importantly, the absence of Cck1 receptor (CCK1R) in <jats:italic>Pcp2-ATXN1[30Q]D776<\/jats:italic> mice conferred a progressive degenerative disease with Purkinje cell loss. Administration of a CCK1R agonist to <jats:italic>Pcp2-AXTN1[82Q]<\/jats:italic> mice reduced Purkinje cell pathology and associated deficits in motor performance. In addition, administration of the CCK1R agonist improved motor performance of <jats:italic>Pcp2-ATXN2[127Q]<\/jats:italic> SCA2 mice. Furthermore, CCK1R activation corrected mTORC1 signaling and improved the expression of calbindin in the cerebella of <jats:italic>AXTN1[82Q]<\/jats:italic> and <jats:italic>ATXN2[127Q]<\/jats:italic> mice. These results support the Cck-Cck1R pathway is a potential therapeutic target for the treatment of diseases involving Purkinje neuron degeneration.<\/jats:p>","DOI":"10.1007\/s12311-022-01428-x","type":"journal-article","created":{"date-parts":[[2022,6,23]],"date-time":"2022-06-23T03:34:22Z","timestamp":1655955262000},"page":"756-760","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Cholecystokinin Activation of Cholecystokinin 1 Receptors: a Purkinje Cell Neuroprotective Pathway"],"prefix":"10.1007","volume":"22","author":[{"given":"Harry T.","family":"Orr","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,6,23]]},"reference":[{"key":"1428_CR1","doi-asserted-by":"publisher","first-page":"630","DOI":"10.1007\/s12311-010-0182-9","volume":"11","author":"AW Kasumu","year":"2012","unstructured":"Kasumu AW, Bezprozvanny I. 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