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Human and mouse neuroinflammation markers in Niemann-Pick disease, type C1.

Cologna SM, Cluzeau CV, Yanjanin NM, Blank PS, Dail MK, Siebel S, Toth CL, Wassif CA, Lieberman AP, Porter FD
J Inherit Metab Dis. 2014 37 (1): 83-92

PMID: 23653225 · PMCID: PMC3877698 · DOI:10.1007/s10545-013-9610-6

Niemann-Pick disease, type C1 (NPC1) is an autosomal recessive lipid storage disorder in which a pathological cascade, including neuroinflammation occurs. While data demonstrating neuroinflammation is prevalent in mouse models, data from NPC1 patients is lacking. The current study focuses on identifying potential markers of neuroinflammation in NPC1 from both the Npc1 mouse model and NPC1 patients. We identified in the mouse model significant changes in expression of genes associated with inflammation and compared these results to the pattern of expression in human cortex and cerebellar tissue. From gene expression array analysis, complement 3 (C3) was increased in mouse and human post-mortem NPC1 brain tissues. We also characterized protein levels of inflammatory markers in cerebrospinal fluid (CSF) from NPC1 patients and controls. We found increased levels of interleukin 3, chemokine (C-X-C motif) ligand 5, interleukin 16 and chemokine ligand 3 (CCL3), and decreased levels of interleukin 4, 10, 13 and 12p40 in CSF from NPC1 patients. CSF markers were evaluated with respect to phenotypic severity. Miglustat treatment in NPC1 patients slightly decreased IL-3, IL-10 and IL-13 CSF levels; however, further studies are needed to establish a strong effect of miglustat on inflammation markers. The identification of inflammatory markers with altered levels in the cerebrospinal fluid of NPC1 patients may provide a means to follow secondary events in NPC1 disease during therapeutic trials.

MeSH Terms (27)

1-Deoxynojirimycin Adolescent Alleles Animals Biomarkers Brain Cerebellum Cerebral Cortex Chemokine CCL3 Chemokine CXCL5 Child Child, Preschool Complement C3 Disease Models, Animal Female Gene Expression Regulation Humans Infant Infant, Newborn Inflammation Interleukins Male Mice Mice, Inbred BALB C Mice, Transgenic Niemann-Pick Disease, Type C Young Adult

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