CHEMICAL PROTEOMIC ANALYSIS OF ENDOCANNABINOID HYDROLASE ACTIVITY IN NIEMANN-PICK TYPE C MOUSE BRAIN

ABSTRACT: The endocannabinoid system is considered to be an endogenous protective system in various neurodegenerative diseases. Niemann-Pick Type C is a neurodegenerative disease in which the role of the endocannabinoid system has not been studied yet. Here, we report the endocannabinoid hydrolase activity in brain proteomes of a Niemann-Pick type C mouse model as measured by activity-based protein profiling. Diacylglycerol lipase α, α/β-hydrolase domain-containing protein 4 (ABHD4), ABHD6, ABHD12, fatty acid amide hydrolase and monoacylglycerol lipase activities were quantified. Chemical proteomics showed no difference in endocannabinoid hydrolase activity in the brain of wildtype compared to Niemann-Pick C1 protein (NPC1) knockout mice. Three lysosomal serine hydrolases were identified with increased activity in NPC1 knockout mouse brain: retinoid-inducible serine carboxypeptidase, cathepsin A and palmitoyl-protein thioesterase 1, and we conclude that these might be interesting therapeutic targets for future validation studies.

INSTRUMENT(S): LTQ Orbitrap, Synapt MS

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

SUBMITTER: Bogdan Florea  

LAB HEAD: Mario van der Stelt

PROVIDER: PXD008979 | Pride | 2018-04-19

REPOSITORIES: Pride