{"doi":"10.1002/pmic.202200378","title":"A differential proteomics study of cerebrospinal fluid from individuals with Niemann‐Pick disease, Type C1","abstract":"Niemann-Pick, type C1 (NPC1) is a fatal, neurodegenerative disease, which belongs to the family of lysosomal diseases. In NPC1, endo/lysosomal accumulation of unesterified cholesterol and sphingolipids arise from improper intracellular trafficking resulting in multi-organ dysfunction. With the proximity between the brain and cerebrospinal fluid (CSF), performing differential proteomics provides a means to shed light to changes occurring in the brain. In this study, CSF samples obtained from NPC1 individuals and unaffected controls were used for protein biomarker identification. A subset of these individuals with NPC1 are being treated with miglustat, a glycosphingolipid synthesis inhibitor. Of the 300 identified proteins, 71 proteins were altered in individuals with NPC1 compared to controls including cathepsin D, and members of the complement family. Included are a report of 10 potential markers for monitoring therapeutic treatment. We observed that pro-neuropeptide Y (NPY) was significantly increased in NPC1 individuals relative to healthy controls; however, individuals treated with miglustat displayed levels comparable to healthy controls. In further investigation, NPY levels in a NPC1 mouse model corroborated our findings. We posit that NPY could be a potential therapeutic target for NPC1 due to its multiple roles in the central nervous system such as attenuating neuroinflammation and reducing excitotoxicity.","journal":"PROTEOMICS","year":2023,"id":352238,"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":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9534,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":516152,"name":"Melissa R. Pergande","orcid":"0000-0003-1197-4057","position":1,"is_corresponding":false},{"id":1098193,"name":"Christopher A. Crutchfield","orcid":null,"position":2,"is_corresponding":false},{"id":237002,"name":"Brian C. Searle","orcid":"0000-0001-8760-6731","position":3,"is_corresponding":false},{"id":365873,"name":"Peter S. Backlund","orcid":null,"position":4,"is_corresponding":false},{"id":843986,"name":"Jaqueline A. Picache","orcid":"0000-0002-1948-9243","position":5,"is_corresponding":false},{"id":1098194,"name":"Kathryn R. Burkert","orcid":null,"position":6,"is_corresponding":false},{"id":1098195,"name":"Nicole M. Yanjanin‐Farhat","orcid":null,"position":7,"is_corresponding":false},{"id":888213,"name":"Paul S. Blank","orcid":"0000-0002-6285-4277","position":8,"is_corresponding":false},{"id":606058,"name":"Cynthia L. Toth","orcid":null,"position":9,"is_corresponding":false},{"id":323700,"name":"Christopher A. Wassif","orcid":"0000-0002-2524-1420","position":10,"is_corresponding":false},{"id":305578,"name":"Forbes D. Porter","orcid":"0000-0001-9397-0046","position":11,"is_corresponding":false},{"id":421639,"name":"Stephanie M. Cologna","orcid":"0000-0002-3541-3361","position":12,"is_corresponding":false},{"id":824179,"name":"Wenping Li","orcid":"0000-0001-5917-5380","position":0,"is_corresponding":true}],"reference_count":73,"raw_metadata":null,"created_at":"2026-07-19T01:12:50.107998Z","pmid":"36638187","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":[]}