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Finding New Drug Targets for Niemann Pick Type C Hepatic Disease Based On Proteomic Network Analysis

ABSTRACT: A significant area of rare diseases research is the investigation of druggable protein encoding genes that contribute to pathogenesis. Niemann Pick Type C (NPC) disease can be considered as a challenging one, among all rare diseases, because it has been associated with a poor prognosis and an unclear molecular pathogenesis. In recent years, Proteomics analysis has become a functional and useful technology for profiling protein expression and find possible drugs targets. In the present study, hepatocytes derived from wild type and Npc1 deficient mice were analyzed by mass spectrometry-based proteomics, followed by pathway analysis and statistical interpretation, performed with the QIAGEN Ingenuity Pathway Analysis (IPA) software. Applications for protein function was built using IPA and gene ontology analysis. We identified and reliably quantified a total of 3833 proteins, among them 416 presented a significant p-value (<0.05) being classified 149 as upregulated (log2 fold change >1) and 6 as downregulated (Log2 fold change <-1). Our analysis revealed that the most significant changed proteins are related to liver damage, lipid metabolism and inflammatory response. In addition, in the group of up/downregulated proteins, 47 proteins were identified as lysosomal proteins and 22 as mitochondrial proteins. Importantly, we found that of those proteins CTSB, LIPA, DPP7, GLMP and DECR1 are related to liver fibrosis, liver damage and steatosis.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Hepatocyte, Liver, Cell Culture

DISEASE(S): Niemann-pick Disease Type C1

SUBMITTER: Robert Hardt

LAB HEAD: Dominic Winter

PROVIDER: PXD026623 | Pride | 2021-08-23

REPOSITORIES: Pride

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			Action	DRS
	181220_TB_chile_pH11.raw	Raw
	181220_TB_chile_pH3.raw	Raw
	181220_TB_chile_pH4.raw	Raw
	181220_TB_chile_pH5.raw	Raw
	181220_TB_chile_pH6.raw	Raw

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