Affiliation:
1. Department of Chemistry University of Illinois Chicago Chicago Illinois USA
2. Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health Bethesda Maryland USA
3. Department of Biomedical Informatics The Ohio State University Medical Center Columbus Ohio USA
Abstract
AbstractNiemann‐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.
Funder
National Niemann-Pick Disease Foundation
Eunice Kennedy Shriver National Institute of Child Health and Human Development
National Institute of Neurological Disorders and Stroke
Subject
Molecular Biology,Biochemistry
Cited by
2 articles.
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