PXD043716

PXD043716 is an original dataset announced via ProteomeXchange.

Title	Proteomics analysis of the brain from a Gaucher disease mouse identifies pathological pathways including a possible role for transglutaminase 1
Description	Gaucher disease (GD) is caused by the defective activity of acid beta-glucosidase (GCase) which results from mutations in GBA1. Neurological forms of GD (nGD) can be generated in mice by intra-peritoneal injection of conduritol B-epoxide (CBE) which irreversibly inhibits GCase. Using this approach, a number of pathological pathways have been identified in mouse brain by RNAseq analysis. However, unlike transcriptomics, proteomics gives information about protein expression which is more likely to provide insight into which cellular pathways may be impacted in disease. We now perform non-targeted, mass spectrometry based quantitative proteomics on brains from mice injected with 50 mg/kg body weight CBE for 13 days. Of the 5,038 detected proteins, 472 were differentially-expressed between control (PBS-injected) and CBE-injected mice of which 104 were selected for further analysis based on higher stringency criteria. Some lysosomal proteins were up-regulated as was interferon signaling, whereas levels of ion channel related proteins and some proteins associated with neurotransmitter signaling were reduced, as was cholesterol metabolism. One protein, transglutaminase 1 (TGM1), which is elevated in a number of neurodegenerative diseases, was absent from the control group, but was found at high levels in CBE-injected mice, and appeared to be located extracellularly in layer V of the cortex whereas it was located intracellularly in Purkinje cells in the cerebellum. Together, the proteomics data confirms previous RNAseq data and adds additional mechanistic understanding about cellular pathways that may play a role in nGD pathology
HostingRepository	MassIVE
AnnounceDate	2023-12-11
AnnouncementXML	Submission_2023-12-11_01:40:54.908.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Meital Kupervaser
SpeciesList	scientific name: Mus musculus; common name: house mouse; NCBI TaxID: 10090;
ModificationList	Carbamidomethyl; Oxidation; Deamidated
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2023-07-12 06:00:31	ID requested
⏵ 1	2023-12-11 01:40:55	announced

Blumenreich S, Ben-Yashar DP, Shalit T, Kupervaser M, Milenkovic I, Joseph T, Futerman AH, Proteomics analysis of the brain from a Gaucher disease mouse identifies pathological pathways including a possible role for transglutaminase 1. J Neurochem, 168(1):52-65(2024) [pubmed]

submitter keyword: Gaucher disease, glucosylceramide, proteomics, RNAseq, pathogenesis

Anthony H. Futerman
contact affiliation	Weizmann Institute of Science, Rehovot
contact email	tony.futerman@weizmann.ac.il
lab head
Meital Kupervaser
contact affiliation	Weizmann Institute of Science
contact email	meital.kupervaser@weizmann.ac.il
dataset submitter

MassIVE dataset URI

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