{"doi":"10.1016/j.celrep.2021.109831","title":"Cholecystokinin 1 receptor activation restores normal mTORC1 signaling and is protective to Purkinje cells of SCA mice","abstract":"Spinocerebellar ataxias (SCAs) are a group of genetic diseases characterized by progressive ataxia and neurodegeneration, often in cerebellar Purkinje neurons. A SCA1 mouse model, Pcp2-ATXN1[30Q]D776, has severe ataxia in absence of progressive Purkinje neuron degeneration and death. Previous RNA-seq analyses identify cerebellar upregulation of the peptide hormone cholecystokinin (Cck) in Pcp2-ATXN1[30Q]D776 mice. Importantly, absence of Cck1 receptor (Cck1R) in Pcp2-ATXN1[30Q]D776 mice confers a progressive disease with Purkinje neuron death. Administration of a Cck1R agonist, A71623, to Pcp2-ATXN1[30Q]D776;Cck−/− and Pcp2-AXTN1[82Q] mice dampens Purkinje neuron pathology and associated deficits in motor performance. In addition, A71623 administration improves motor performance of Pcp2-ATXN2[127Q] SCA2 mice. Moreover, the Cck1R agonist A71623 corrects mTORC1 signaling and improves expression of calbindin in cerebella of AXTN1[82Q] and ATXN2[127Q] mice. These results indicate that manipulation of the Cck-Cck1R pathway is a potential therapeutic target for treatment of diseases involving Purkinje neuron degeneration.","journal":"Cell Reports","year":2021,"id":188022,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":17,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9486,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":527019,"name":"Chen Zhao","orcid":"0000-0003-1373-7637","position":1,"is_corresponding":false},{"id":485377,"name":"Sharan Paul","orcid":"0000-0002-9845-3125","position":2,"is_corresponding":false},{"id":506198,"name":"Praseuth Yang","orcid":"0000-0002-4094-9435","position":3,"is_corresponding":false},{"id":485379,"name":"Karla P. Figueroa","orcid":"0000-0003-4857-9288","position":4,"is_corresponding":false},{"id":748987,"name":"Jill Friedrich","orcid":null,"position":5,"is_corresponding":false},{"id":748988,"name":"Tyler Tschumperlin","orcid":null,"position":6,"is_corresponding":false},{"id":748321,"name":"Michael Berken","orcid":"0000-0002-9923-0679","position":7,"is_corresponding":false},{"id":748989,"name":"Melissa Ingram","orcid":null,"position":8,"is_corresponding":false},{"id":267854,"name":"Christine Henzler","orcid":"0000-0003-4566-2211","position":9,"is_corresponding":false},{"id":291788,"name":"Stefan M. Pulst","orcid":"0000-0003-0883-7879","position":10,"is_corresponding":false},{"id":262866,"name":"Harry T. Orr","orcid":"0000-0001-6118-741X","position":11,"is_corresponding":false},{"id":748986,"name":"Emily A.L. Wozniak","orcid":null,"position":0,"is_corresponding":true}],"reference_count":40,"raw_metadata":null,"created_at":"2026-07-18T23:49:05.976005Z","pmid":"34644575","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}